rs137853010

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_ModerateBS2_Supporting

The NM_007194.4(CHEK2):c.541C>T(p.Arg181Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000806 in 1,613,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. 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. R181H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000083 ( 0 hom. )

Consequence

CHEK2
NM_007194.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1U:24B:1

Conservation

PhyloP100: 2.67

Publications

26 publications found

Variant links:

Genes affected

CHEK2 (HGNC:16627): (checkpoint kinase 2) In response to DNA damage and replication blocks, cell cycle progression is halted through the control of critical cell cycle regulators. The protein encoded by this gene is a cell cycle checkpoint regulator and putative tumor suppressor. It contains a forkhead-associated protein interaction domain essential for activation in response to DNA damage and is rapidly phosphorylated in response to replication blocks and DNA damage. When activated, the encoded protein is known to inhibit CDC25C phosphatase, preventing entry into mitosis, and has been shown to stabilize the tumor suppressor protein p53, leading to cell cycle arrest in G1. In addition, this protein interacts with and phosphorylates BRCA1, allowing BRCA1 to restore survival after DNA damage. Mutations in this gene have been linked with Li-Fraumeni syndrome, a highly penetrant familial cancer phenotype usually associated with inherited mutations in TP53. Also, mutations in this gene are thought to confer a predisposition to sarcomas, breast cancer, and brain tumors. This nuclear protein is a member of the CDS1 subfamily of serine/threonine protein kinases. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

CHEK2 Gene-Disease associations (from GenCC):

CHEK2-related cancer predisposition
Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics
hereditary breast carcinoma
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
Li-Fraumeni syndrome 2
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
acute myeloid leukemia
Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
hereditary nonpolyposis colon cancer
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
familial ovarian cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

CHEK2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.16097897).

BS2

High AC in GnomAd4 at 9 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHEK2	NM_007194.4 link	c.541C>T	p.Arg181Cys	missense_variant	Exon 4 of 15	ENST00000404276.6	NP_009125.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHEK2	ENST00000404276.6 link	c.541C>T	p.Arg181Cys	missense_variant	Exon 4 of 15	1	NM_007194.4	ENSP00000385747.1

Frequencies

GnomAD3 genomes

AF:

0.0000593

AC:

AN:

151874

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000111

AC:

AN:

251404

AF XY:

0.000132

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000616

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000828

AC:

121

AN:

1461776

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

727188

show subpopulations

African (AFR)

AF:

0.0000896

AC:

AN:

33476

American (AMR)

AF:

0.0000894

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39682

South Asian (SAS)

AF:

0.000510

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000585

AC:

AN:

1111924

Other (OTH)

AF:

0.0000828

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000593

AC:

AN:

151874

Hom.:

Cov.:

AF XY:

0.0000809

AC XY:

AN XY:

74146

show subpopulations

African (AFR)

AF:

0.0000484

AC:

AN:

41334

American (AMR)

AF:

0.000131

AC:

AN:

15216

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000208

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10566

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

67972

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.0000647

Hom.:

Bravo

AF:

0.0000302

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000988

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1Uncertain:24Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Familial cancer of breast

Uncertain:9

Mar 09, 2023

Myriad Genetics, Inc.

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk. -

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 181 of the CHEK2 protein (p.Arg181Cys). This variant is present in population databases (rs137853010, gnomAD 0.05%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with CHEK2-related conditions (PMID: 18058223, 18996005, 22419737, 29522266, 36468172). ClinVar contains an entry for this variant (Variation ID: 5597). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on CHEK2 function (PMID: 16835864, 22419737, 30851065). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

May 03, 2020

Genomic Research Center, Shahid Beheshti University of Medical Sciences

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 13, 2022

MGZ Medical Genetics Center

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 24, 2024

Baylor Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 16, 2025

Molecular Pathology, Peter Maccallum Cancer Centre

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 29, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

a variant of uncertain significance was detected in the CHEK2 gene (c.541C>T). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 181 of the CHEK2 protein (p.Arg181Cys).This amino acid position is poorly conserved(PhyloP=2.3). This variant is present in population databases (rs137853010, gnomAD 0.05%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with breast, ovarian and colorectal cancer (PMID: 18058223, 18996005, 22419737, 29522266). ClinVar contains an entry for this variant (Variation ID: 5597). In addition, this alteration is predicted to be tolerated by in silico analysis. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Apr 23, 2024

Institute of Human Genetics, University of Leipzig Medical Center

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Criteria applied: PM5 -

Nov 08, 2016

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. -

not provided

Uncertain:6

Oct 23, 2024

Quest Diagnostics Nichols Institute San Juan Capistrano

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The CHEK2 c.541C>T (p.Arg181Cys) variant has been reported in the published literature in individuals affected with breast cancer (PMID: 34711244 (2021), 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared)), 32923877 (2020), 29522266 (2018), 28779002 (2017), 22419737 (2012), 18058223 (2008)), prostate cancer (PMID: 29520813 (2018), 16835864 (2006)), colon/rectal cancer (PMID: 34711244 (2021), 18996005 (2009)), and pediatric B-cell acute lymphoblastic leukemia (B-ALL) (PMID: 36468172 (2023)). This variant has also been observed in reportedly healthy individuals (PMID: 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared)), 31050813 (2019), 30287823 (2018)). Assessment of experimental evidence regarding the effect of this variant on protein function is inconclusive (PMID: 36468172 (2023), 31050813 (2019), 30851065 (2019), 22419737 (2012), 16835864 (2006)). The frequency of this variant in the general population, 0.00052 (16/30612 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 conflicting predictions that this variant is deleterious or benign. Based on the available information, we are unable to determine the clinical significance of this variant. -

Nov 03, 2021

Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

May 27, 2022

Clinical Genetics Laboratory, Skane University Hospital Lund

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 26, 2025

GeneDx

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

In silico analysis indicates that this missense variant does not alter protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); Also known as c.670C>T p.(R224C); Published functional studies are conflicting: some show reduced response to DNA damage and kinase activity, while others show kinase activity and DNA damage response comparable to wild-type (PMID: 16835864, 22419737, 30851065, 31050813, 37449874); Observed in individuals with CHEK2-related cancers, but also in unaffected controls (PMID: 12533788, 16835864, 16941491, 18058223, 18996005, 28779002, 29522266, 30287823, 29520813, 32923877, 33471991, 34711244, 36243179, 33309985, 32980694, 37449874); This variant is associated with the following publications: (PMID: 26822949, 16835864, 27157322, 12533788, 22419737, 18058223, 16941491, 18996005, 19782031, 21765476, 29520813, 28873162, 30851065, 31050813, 30287823, 34711244, 34426522, 36468172, 28125078, 28779002, 26580448, 29522266, 32923877, 33471991, 32980694, 36243179, 33309985, 32906206, 38630906, 37449874) -

not specified

Uncertain:3

Jul 27, 2022

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

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant summary: CHEK2 c.541C>T (p.Arg181Cys) results in a non-conservative amino acid change located in the Forkhead-associated (FHA) domain (IPR000253) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00011 in 251404 control chromosomes, predominantly at a frequency of 0.00052 within the South Asian subpopulation in the gnomAD database. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 1.7 fold of the estimated maximal expected allele frequency for a pathogenic variant in CHEK2 causing Hereditary Breast and Ovarian Cancer phenotype (0.00031), suggesting that the variant might be a benign polymorphism. c.541C>T has been reported in the literature in individuals affected with prostate-, breast- and colorectal cancer, as well as in pediatric acute lymphoblastic leukemia and Ewing sarcoma, and multiple primary tumors (Dong_2003, Wu_2018, Kleibl_2008, Kleibl_2009, Zhang_2016, Brohl_2017, Dorling_2021, Wallander_2021), however it was also reported in several unaffected controls (Momozawa_2018, Kleiblova_2019, Narang_2020, Dorling_2021, Mizukami_2020). These reports therefore do not provide unequivocal conclusions about association of the variant with the disease. Several publications reported experimental evidence evaluating an impact on protein function, and demonstrated for the variant protein unaffected autophosphorylation, but partially reduced kinase activity in a mammalian cell system (Wu_2006), as well as an intermediate response to DNA damage in a yeast complementation assay (Roeb_2012). However later studies reported the variant to be similar to WT in a yeast complementation assay (Delimitsou_2019) and with unaffected kinase activity in mammalian cells (Kleiblova_2019). Nine other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014, and all of them classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly benign. -

Jun 10, 2022

Genetic Services Laboratory, University of Chicago

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:clinical testing

DNA sequence analysis of the CHEK2 gene demonstrated a sequence change, c.541C>T, in exon 4 that results in an amino acid change, p.Arg181Cys. This sequence change has been previously described in one individual with prostate cancer (PMID: 29520813) and has been described in the gnomAD database with a frequency of 0.011% in the overall population (dbSNP rs137853010). The p.Arg181Cys change affects a poorly conserved amino acid residue located in a domain of the CHEK2 protein that is known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Arg181Cys substitution. Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Arg181Cys change remains unknown at this time. -

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary cancer-predisposing syndrome

Uncertain:3

Sep 23, 2024

Color Diagnostics, LLC DBA Color Health

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This missense variant replaces arginine with cysteine at codon 181 of the CHEK2 protein. Computational prediction suggests that this variant may not impact protein structure and function. Functional studies have shown conflicting results, showing the mutant protein to be functional in in vitro kinase and DNA damage response assays (PMID: 16835864, 30851065, 31050813, 36468172, 37449874), but also exhibit partially reduced activity (PMID: 22419737), or no activity (PMID: 36468172) in similar assays. This variant has been reported in individuals affected with breast cancer (PMID: 18058223, 22419737, 29522266, 34711244), colorectal cancer (PMID: 18996005, 34711244), prostate cancer (PMID: 12533788, 16835864, 29520813), and other hereditary cancers (PMID: 26580448, 28873162, 36468172). This variant did not show a significant association with breast cancer in two case control studies (PMID: 33471991, OR=1.768, 95%CI 0.442 to 7.07; PMID: 37449874, OR 1.70 (0.77-3.86). This variant has been identified in 31/282774 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. -

Dec 08, 2021

Sema4, Sema4

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:curation

- -

Aug 15, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The p.R181C variant (also known as c.541C>T), located in coding exon 3 of the CHEK2 gene, results from a C to T substitution at nucleotide position 541. The arginine at codon 181 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration has been reported in individuals diagnosed with breast cancer, colorectal cancer, and/or prostate cancer (Zheng L et al. Hum. Mutat. 2006 Oct;27:1062-3; Wu Y et al. Prostate. 2018 Jun;78:607-615; Kleibl Z et al. Breast Cancer Res. Treat. 2008 Nov;112:159-64; Hauke J et al. Cancer Med. 2018 Apr;7:1349-1358; Kleibl Z et al. Eur. J. Cancer. 2009 Mar;45:618-24). Several yeast-based functional studies have reported this variant to result in a partial reduction in activity (Wu X et al. Hum. Mutat. 2006 Aug;27:742-7; Roeb W et al. Hum. Mol. Genet. 2012 Jun;21:2738-44), while other functional studies conducted in yeast and human cell lines have reported this variant to have a neutral impact on CHEK2 activity (Delimitsou A et al. Hum Mutat. 2019 May;40(5):631-648; Kleiblova P et al. Int J Cancer. 2019 Oct;145(7):1782-1797; Stolarova L et al. Clin Cancer Res. 2023 Aug;29(16):3037-3050). This amino acid position is poorly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. -

Prostate cancer, somatic

Pathogenic:1

Feb 01, 2003

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

CHEK2-related disorder

Uncertain:1

Jun 19, 2024

PreventionGenetics, part of Exact Sciences

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:clinical testing

The CHEK2 c.541C>T variant is predicted to result in the amino acid substitution p.Arg181Cys. This variant has been reported in individuals with a history of colorectal, breast, or prostate cancers and was absent from control cohorts (Dong et al. 2003. PubMed ID: 12533788; Wu et al. 2006. PubMed ID: 16835864; Kleibl et al. 2008. PubMed ID: 18058223; Kleibl et al. 2009. PubMed ID: 18996005; Wu et al. 2018. PubMed ID: 29520813). Functional assays have demonstrated that this variant impacts CHEK2 kinase activity and has an intermediate response to DNA damage (Roeb et al. 2012. PubMed ID: 22419737; Wu et al. 2006. PubMed ID: 16835864). Results of an in vivo, yeast‐based, functional assay indicated that this variant did not impact growth, which suggests this allele may be functional (i.e. benign) (Delimitsou et al. 2019. PubMed ID: 30851065). This variant is reported in 0.052% of alleles in individuals of South Asian descent in gnomAD and is interpreted as uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/5597/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Predisposition to cancer

Uncertain:1

Jun 17, 2025

St. Jude Molecular Pathology, St. Jude Children's Research Hospital

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The CHEK2 c.541C>T p.(Arg181Cys) missense change has a maximum subpopulation frequency of 0.05% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org). The in silico tool REVEL is inconclusive about a pathogenic or benign effect of this variant on protein function and functional studies are conflicting (PMID: 16835864, 22419737, 30851065, 31050813). This variant has been reported in individuals with prostate cancer, breast cancer, and colorectal cancer (PMID: 12533788, 16835864, 18058223, 18996005, 22419737, 29522266, 34711244). In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. -

CHEK2-related cancer predisposition

Uncertain:1

Apr 03, 2024

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary breast ovarian cancer syndrome

Benign:1

Nov 12, 2024

German Consortium for Hereditary Breast and Ovarian Cancer, University Hospital Cologne

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:curation

According to the ACMG SVI adaptation criteria we chose these criteria: BS1 (supporting benign): gnomAD v2 (non-cancer) South Asian 0,05%, BS3 (strong benign): Storalova (PMID: 37449874) & Delimitsou (PMID: 30851065) benign -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.088

BayesDel_noAF

Uncertain

-0.020

CADD

Benign

(source)

DANN

Uncertain

0.97

DEOGEN2

Benign

0.36

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

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.91

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

M_CAP

Benign

0.054

MetaRNN

Benign

0.16

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.41

MutationAssessor

Benign

1.6

L;L;L;L;.;L;L;.;.

PhyloP100

2.7

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.7

N;N;N;N;N;.;N;N;.

REVEL

Uncertain

0.47

Sift

Benign

0.20

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

Sift4G

Benign

0.20

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

Polyphen

0.0020

B;B;B;B;B;B;B;.;.

Vest4

0.44

MVP

0.92

MPC

0.022

ClinPred

0.026

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.28

gMVP

0.49

Mutation Taster

=3/97

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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