1-45332479-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM1PP5

The NM_001128425.2(MUTYH):c.700G>A(p.Val234Met) variant causes a missense change. The variant allele was found at a frequency of 0.00025 in 1,613,998 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V234L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00026 ( 0 hom. )

Consequence

MUTYH
NM_001128425.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:12U:8

Conservation

PhyloP100: 4.56

Publications

16 publications found

Variant links:

COSMIC-nc: COSV58345221

Genes affected

MUTYH (HGNC:7527): (mutY DNA glycosylase) This gene encodes a DNA glycosylase involved in oxidative DNA damage repair. The enzyme excises adenine bases from the DNA backbone at sites where adenine is inappropriately paired with guanine, cytosine, or 8-oxo-7,8-dihydroguanine, a major oxidatively damaged DNA lesion. The protein is localized to the nucleus and mitochondria. This gene product is thought to play a role in signaling apoptosis by the introduction of single-strand breaks following oxidative damage. Mutations in this gene result in heritable predisposition to colorectal cancer, termed MUTYH-associated polyposis (MAP). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2017]

MUTYH Gene-Disease associations (from GenCC):

familial adenomatous polyposis 2
Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen, G2P
colorectal cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
familial ovarian cancer
Inheritance: AD, AR Classification: NO_KNOWN Submitted by: ClinGen
hereditary breast carcinoma
Inheritance: AD, AR Classification: NO_KNOWN Submitted by: ClinGen

MUTYH links:

ENSG00000288208 (HGNC:):

ENSG00000288208 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM1

In a hotspot region, there are 9 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 43 uncertain in NM_001128425.2

PP5

Variant 1-45332479-C-T is Pathogenic according to our data. Variant chr1-45332479-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 135989.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUTYH	NM_001128425.2 link	c.700G>A	p.Val234Met	missense_variant	Exon 9 of 16	ENST00000710952.2	NP_001121897.1
MUTYH	NM_001048174.2 link	c.616G>A	p.Val206Met	missense_variant	Exon 9 of 16	ENST00000456914.7	NP_001041639.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
MUTYH	ENST00000710952.2 link	c.700G>A	p.Val234Met	missense_variant	Exon 9 of 16		NM_001128425.2	ENSP00000518552.2
MUTYH	ENST00000456914.7 link	c.616G>A	p.Val206Met	missense_variant	Exon 9 of 16	1	NM_001048174.2	ENSP00000407590.2
ENSG00000288208	ENST00000671898.1 link	n.1204G>A		non_coding_transcript_exon_variant	Exon 13 of 21			ENSP00000499896.1

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000758

AC:

AN:

250668

AF XY:

0.0000590

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000168

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000261

AC:

381

AN:

1461778

Hom.:

Cov.:

AF XY:

0.000246

AC XY:

179

AN XY:

727184

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53350

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000317

AC:

353

AN:

1111982

Other (OTH)

AF:

0.000464

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

104

130

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000151

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41462

American (AMR)

AF:

0.0000654

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000309

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000124

Hom.:

Bravo

AF:

0.000128

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000123

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000237

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:12Uncertain:8

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Familial adenomatous polyposis 2

Pathogenic:7Uncertain:2

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 234 of the MUTYH protein (p.Val234Met). This variant is present in population databases (rs200165598, gnomAD 0.02%). This missense change has been observed in individual(s) with colon cancer and/or clinical features of MUTYH-associated polyposis (MAP) (PMID: 14991577, 16774938, 30374176; internal data). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as c.658G>A (p.Val220Met). ClinVar contains an entry for this variant (Variation ID: 135989). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects MUTYH function (PMID: 25820570, 26694661). For these reasons, this variant has been classified as Pathogenic. -

Mar 11, 2024

Baylor Genetics

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 16, 2018

University of Washington Department of Laboratory Medicine, University of Washington

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:research

The MUTYH variant designated as NM_001128425.1:c.700G>A (p.Val234Met) is classified as likely pathogenic. In one observed family, this variant co-occurs with a known pathogenic variant (MUTYH p.Tyr179Cys or p.Y179C) in MUTYH in five siblings who each have a documented history of multiple colon polyps and/or colon cancer. The variant was shown to be in trans configuration with the MUTYH p.Y179C variant. This genomic position is highly conserved. Experimental studies of this variant have shown that it partially impairs MUTYH protein function (Komine 2015, PMID: 25820570). This variant is listed in population databases and is present in 1/5500 individuals of European descent (exac.broadinstitute.org). Bayesian analysis integrating all of this data (Tavtigian et al, 2018) gives about 98% probability of pathogenicity, which is consistent with a classification of likely pathogenic. MUTYH p.Val234Met is expected to alter MUTYH function and increase the risk of developing colon cancer, multiple colon polyps, and other features of MYH-associated polyposis when it co-occurs with a pathogenic mutation in MUTYH (Morak 2010, PMID 20618354; Grover 2012, PMID: 22851115). This analysis was performed in conjunction with the family studies project as part of the University of Washington Find My Variant Study. -

Sep 27, 2024

All of Us Research Program, National Institutes of Health

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This missense variant replaces valine with methionine at codon 234 of the MUTYH protein (NM_001128425.1). This variant has also been reported as Val206Met in the context of an alternative transcript (NM_001048174.2). Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). A functional study has shown the mutant protein to exhibit a partial defect in DNA mismatch repair assay in a bacterial system (PMID: 25820570) but a near normal DNA mismatch repair activity in human cells despite partially reduced DNA glycosylase activity (PMID: 26694661). This variant has been reported in the compound heterozygous state with two different pathogenic MUTYH variants in two unrelated individuals affected with colorectal polyposis and cancer (PMID: 20618354, 30374176). For one of these probands, the same biallelic mutations were observed in four other siblings also affected with colorectal polyposis and cancer (PMID: 30374176). Additional individuals affected with colorectal polyposis and/or cancer who carried another disease causing variant in the same gene in addition to this variant have been reported by external laboratories (ClinVar SCV000211403.14, SCV000186820.7, external communication). This variant has also been observed in heterozygous individuals affected with colorectal cancer (PMID: 14991577, 16774938, 25980754). This variant has been identified in 24/282044 chromosomes (23/128662 Non-Finnish European chromosomes) in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Likely Pathogenic. -

Nov 18, 2015

Counsyl

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:clinical testing

This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. -

Sep 19, 2023

Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 19, 2024

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant summary: MUTYH c.700G>A (p.Val234Met) results in a conservative amino acid change located in the DNA-glycosylase domain (IPR011257) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00025 in 1613998 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in MUTYH causing MUTYH-Associated Polyposis (0.00025 vs 0.0046), allowing no conclusion about variant significance. c.700G>A has been reported in the literature in individuals affected with Lynch syndrome, pancreatic cancer, relapsed pediatric acute myeloid leukemia, endometrial cancer without strong evidence for causality, or in a patient affected with colon cancer (e.g. Fleischmann 2004, Peterlongo 2006, Yurgelun 2015, Dudley_2018, Umeda_2022, Gordhandas_2023). It has also been observed as a biallelic compound heterozygous genotype with another pathogenic MUTYH variant in at-least 5 informative individuals in a family with clinical features of MUTYH-associated polyposis (c.536A>G/p.Y179C) (e.g. Tsai_2019, Young_2024) and at our laboratory (internal data). These data indicate that the variant is likely to be associated with disease in recessive pattern. One functional study in which the variant was expressed in MutY-disrupted Escherichia coli showed the variant to be partially defective, resulting in 2-fold higher spontaneous mutation rates compared to WT (Komine 2015). However, other functional studies found the variant to have only slightly impaired mismatch repair activity in human cells (e.g. Shinmura 2016, Young_2024). The following publications have been ascertained in the context of this evaluation (PMID: 29360161, 14991577, 38397143, 25820570, 16774938, 26694661, 30374176, 35176137, 38196581, 25980754, 26580448). ClinVar contains an entry for this variant (Variation ID: 135989). Based on the evidence outlined above, the variant was classified as pathogenic. -

Jun 07, 2021

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The p.Val234Met variant in MUTYH has been reported in at least 3 individuals with colorectal cancer (Fleischmann 2004 PMID: 14991577, Peterlongo 2006 PMID: 16774938, Tsai 2019 PMID: 30374176). In one family, the variant was identified in trans with the pathogenic p.Tyr179Cys variant and these variants segregated in 4 affected siblings who had colon cancer or polyposis (Tsai 2019 PMID: 30374176). Furthermore, this variant has also been reported by one clinical laboratory in ClinVar in an individual with a personal and family history of colon cancer who also harbored a pathogenic MUTYH frameshift variant (ClinVar variation ID 135989, SCV001159672.1). In vitro functional studies are contradictory with one study providing evidence that the p.Val234Met variant may impact protein function (Komine 2015, PMID: 25820570), while another study showed that the protein function is fully retained (Shinmura 2016, PMID: 26694661). However, these types of assays may not accurately represent biological function. This variant has been identified in 0.01% (23/128662) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org); however, this frequency is low enough to be consistent with a recessive carrier frequency. Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied: PM3, PM2_Supporting, PP1_Moderate. -

Jun 07, 2024

Molecular Pathology, Peter Maccallum Cancer Centre

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Pathogenic:2Uncertain:2

Sep 28, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The MUTYH c.700G>A; p.Val234Met variant (rs200165598), also known as Val220Met for traditional nomenclature, is reported in the literature in individuals with colorectal cancer but a second MUTYH variant was not identified (Fleischmann 2004, Peterlongo 2006, Yurgelun 2015). Our laboratory has identified this variant previously in an individual with a personal and family history of colon cancer, who also carried a pathogenic MUTYH frameshift variant. One functional study shows that the p.Val234Met variant protein has partially defective function (Komine 2015), while another study shows the variant protein retains normal repair activity (Shinmura 2016). This variant is reported in ClinVar (Variation ID: 135989). It is found in the general European (non-Finnish) population with an allele frequency of 0.02% (23/128662 alleles) in the Genome Aggregation Database. Due to limited information, the significance of this variant is uncertain at this time. REFERENCES Fleischmann C et al. Comprehensive analysis of the contribution of germline MYH variation to early-onset colorectal cancer. Int J Cancer. 2004 Apr 20;109(4):554-8. Komine K et al. Functional Complementation Assay for 47 MUTYH Variants in a MutY-Disrupted Escherichia coli Strain. Hum Mutat. 2015 Jul;36(7):704-11. Peterlongo P et al. Increased frequency of disease-causing MYH mutations in colon cancer families. Carcinogenesis. 2006 Nov;27(11):2243-9. Shinmura K et al. Functional Evaluation of Nine Missense-Type Variants of the Human DNA Glycosylase Enzyme MUTYH in the Japanese Population. Hum Mutat. 2016 Apr;37(4):350-3. Yurgelun MB et al. Identification of a Variety of Mutations in Cancer Predisposition Genes in Patients With Suspected Lynch Syndrome. Gastroenterology. 2015 Sep;149(3):604-13.e20. -

Apr 30, 2025

GeneDx

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Observed as heterozygous in individuals with colon cancer as well as in healthy controls (PMID: 16774938, 14991577); Published functional studies demonstrate partially defective base excision repair activity, but DNA glycosylase activity and mutation suppression ability similar to wild-type (PMID: 25820570, 26694661); In silico analysis indicates that this missense variant does not alter protein structure/function; Also known as c.658G>A p.(V220M); This variant is associated with the following publications: (PMID: 19725997, 20725929, 14991577, 16774938, 25820570, 15465463, 25980754, 26694661, 28944238, 33436027, 29360161, 26580448, 26377631, 15326180, 9846876, 17581577, 17161978, 35034041, 37357966, 33471991, 38196581, 33850299, 34326862, 36744932, 31422818, 23108399, 11801590, 30374176) -

Jul 25, 2017

PreventionGenetics, part of Exact Sciences

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 21, 2024

Quest Diagnostics Nichols Institute San Juan Capistrano

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The MUTYH c.700G>A (p.Val234Met) variant has been reported in the published literature in individuals affected with Lynch syndrome-associated cancers and/or polyps (PMID: 16774938 (2006), 14991577 (2004), 25980754 (2015), 28944238 (2017), 31422818 (2019), 33436027 (2021)), breast cancer (PMID: 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared)), endometrial cancer (PMID: 36744932 (2023)) and hematological malignancies (PMID: 33850299 (2021)). This variant has also been observed in reportedly healthy individuals (PMID: 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared)). This variant was determined to segregate with disease in five siblings, each of whom were also positive for a known MUTYH pathogenic variant (c.536A>G, p.Tyr179Cys) and a documented history of colon cancer and/or over 20 colonic polyps (PMID: 30374176 (2019)). Functional studies examining the effect of this variant on MUTYH protein function have yielded conflicting results (PMID: 25820570 (2015), 26694661 (2016)). The frequency of this variant in the general population, 0.00018 (23/128662 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, this variant is classified as likely pathogenic. -

Hereditary cancer-predisposing syndrome

Pathogenic:2Uncertain:1

Sep 03, 2024

Ambry Genetics

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The p.V234M variant (also known as c.700G>A), located in exon 9 of the MUTYH gene, results from a G to A substitution at nucleotide position 700. The valine at codon 234 is replaced by methionine, an amino acid with highly similar properties. This variant has been reported in the heterozygous state in multiple colorectal cancer/polyposis and HNPCC/HNPCC-like cohorts to date (Peterlongo P et al. Carcinogenesis. 2006 Nov;27:2243-9; Fleischmann C et al. Int. J. Cancer. 2004 Apr;109:554-8; DeRycke MS et al. Mol Genet Genomic Med, 2017 Sep;5:553-569; Gordon AS et al. Am J Hum Genet, 2019 09;105:526-533; Patel SG et al. Hered Cancer Clin Pract, 2021 Jan;19:8). In two studies, it was reported to have at least partial function in bacterial and human cell-line based glycosylase and mutagenesis assays (Komine K et al. Hum. Mutat. 2015 Jul;36:704-11; Shinmura K et al. Hum. Mutat. 2016 Apr;37:350-3). This variant segregated with colon cancer or colon polyps in five siblings reported to have co-occurrence with a pathogenic MUTYH founder mutation, which was confirmed to be in trans through familial testing (Tsai GJ et al. Genet. Med. 2019 06;21:1435-1442). This variant has also been identified likely in trans with a MUTYH likely pathogenic or pathogenic variant in multiple individuals with clinical features of MUTYH-associated polyposis (Ambry internal data). Based on internal structural analysis, this variant is anticipated to disrupt a region of known function (Ambry internal data; Guan Y et al. Nat. Struct. Biol. 1998 Dec;5:1058-64; Manuel RC et al. J. Biol. Chem. 2004 Nov;279:46930-9). Of note, this variant is also designated as V220M in published literature. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. -

Feb 03, 2025

Color Diagnostics, LLC DBA Color Health

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This missense variant replaces valine with methionine at codon 234 of the MUTYH protein (NM\\_001128425.1). This variant has also been reported as Val206Met in the context of an alternative transcript (NM\\_001048174.2). Computational prediction suggests that this variant may have deleterious impact on protein structure and function. A functional study has shown the mutant protein to exhibit a partial defect in DNA mismatch repair assay in a bacterial system (PMID: 25820570) but a near normal DNA mismatch repair activity in human cells despite partially reduced DNA glycosylase activity (PMID: 26694661). This variant has been reported in the compound heterozygous state with two different pathogenic MUTYH variants in two unrelated individuals affected with colorectal polyposis and cancer (PMID: 20618354, 30374176). For one of these probands, the same biallelic mutations were observed in four other siblings also affected with colorectal polyposis and cancer (PMID: 30374176). Additional individuals affected with colorectal polyposis and/or cancer who carried another disease causing variant in the same gene have been reported by external laboratories (ClinVar SCV000211403.14, SCV000186820.7, external communication). This variant has also been observed in heterozygous individuals affected with colorectal cancer (PMID: 14991577, 16774938, 25980754). This variant has been identified in 24/282044 chromosomes (23/128662 Non-Finnish European chromosomes) in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Likely Pathogenic. -

Dec 20, 2021

Sema4, Sema4

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:curation

- -

Gastric cancer;C3272841:Familial adenomatous polyposis 2

Pathogenic:1Uncertain:1

Feb 02, 2024

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 07, 2024

Fulgent Genetics, Fulgent Genetics

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Uncertain:2

Apr 10, 2019

Genetic Services Laboratory, University of Chicago

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Pathogenic

0.31

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

.;.;.;.;.;T;.;.;.;T;.;T

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

.;D;.;D;D;D;D;D;D;D;D;D

M_CAP

Uncertain

0.20

MetaRNN

Uncertain

0.66

D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Uncertain

0.61

MutationAssessor

Uncertain

2.6

.;.;.;.;.;M;.;.;.;.;.;.

PhyloP100

4.6

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-2.1

N;N;N;N;N;N;N;N;N;N;N;N

REVEL

Pathogenic

0.77

Sift

Uncertain

0.0030

D;T;D;T;D;T;T;T;T;T;D;T

Sift4G

Uncertain

0.0070

D;D;D;D;D;D;D;D;D;D;D;D

Polyphen

0.91, 0.88, 0.81

.;.;.;.;.;P;P;.;P;.;.;.

Vest4

0.93

MVP

0.91

MPC

0.54

ClinPred

0.27

GERP RS

4.6

PromoterAI

-0.013

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.28

gMVP

0.67

Mutation Taster

=0/100

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over