rs200050883

Positions:

• chr22-28695190-C-A
• chr22-28695190-C-G
• chr22-28695190-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6 BS2_Supporting

The NM_007194.4(CHEK2):​c.1312G>T​(p.Asp438Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000376 in 1,613,498 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts 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. D438G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00037 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00038 (2 hom.)
• Consequence: CHEK2 NM_007194.4 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:22 B:10 O:2
• Conservation: PhyloP100: 4.62

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.045587093).
• BP6: Variant 22-28695190-C-A is Benign according to our data. Variant chr22-28695190-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 128056.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=14, Likely_benign=9, not_provided=2}.
• BS2: High Homozygotes in GnomAdExome4 at 2 AD,AR geneVariant has number of homozygotes 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/exons	MANE	UniProt
CHEK2	NM_007194.4	c.1312G>T	p.Asp438Tyr	missense_variant	12/15	ENST00000404276.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHEK2	ENST00000404276.6	c.1312G>T	p.Asp438Tyr	missense_variant	12/15	1	NM_007194.4	P2

Frequencies

GnomAD3 genomes AF: 0.000375 AC: 57 AN: 152144 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00549

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.000754

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000514

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000386 AC: 97 AN: 251038 Hom.: 0 AF XY: 0.000339 AC XY: 46 AN XY: 135660

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000294

Gnomad FIN exome AF: 0.00134

Gnomad NFE exome AF: 0.000459

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.000376 AC: 549 AN: 1461236 Hom.: 2 Cov.: 30 AF XY: 0.000359 AC XY: 261 AN XY: 726952

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000394

Gnomad4 FIN exome AF: 0.00131

Gnomad4 NFE exome AF: 0.000362

Gnomad4 OTH exome AF: 0.000265

GnomAD4 genome AF: 0.000374 AC: 57 AN: 152262 Hom.: 1 Cov.: 32 AF XY: 0.000403 AC XY: 30 AN XY: 74442

Gnomad4 AFR AF: 0.0000963

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.000754

Gnomad4 NFE AF: 0.000514

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000426 Hom.: 1

Bravo AF: 0.000280

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000280 AC: 34

EpiCase AF: 0.00109

EpiControl AF: 0.000593

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:22 Benign:10 Other:2

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Uncertain:9 Benign:2 Other:1

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 26, 2023	Published functional studies are inconclusive/conflicting: demonstrates intermediate/reduced kinase activity in some studies while others, including a human-cell based assay, show activity comparable to wildtype (Bell et al., 2007; Delimitsou et al., 2019; Kleiblova et al., 2019; Boonen et al., 2022); Observed in individuals with a personal and/or family history of breast, prostate, or colorectal cancer (Seppala et al., 2003; Bell et al., 2007; Tischkowitz et al., 2008; Baloch et al., 2014; Tung et al., 2015; Kayser et al., 2018; Fanale et al., 2020; Grasel et al., 2020; Moradian et al., 2021; Paduano et al., 2022); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 14612911, 15087378, 28828701, 28776603, 28873162, 24390236, 17721994, 18571837, 23960188, 21244692, 27067391, 26787654, 28553140, 25186627, 27153395, 27498913, 27878467, 28452373, 19768534, 29335925, 27595995, 27443514, 29987844, 29484706, 30344923, 28301460, 30851065, 29875428, 29522266, 31050813, 31398194, 31159747, 28779002, 31220302, 33134171, 33322746, 32854451, 33558524, 27009842, 32906215, 30613976, 27535533, 34903604, 34347074, 22419737, 19782031, 35886069, 33840814) -
Uncertain significance, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	CHEK2: BP1, BP4, BS2 -
Uncertain significance, criteria provided, single submitter	clinical testing	Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	Nov 03, 2021	- -
Uncertain significance, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Uncertain significance, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Revvity Omics, Revvity	Jun 14, 2023	- -
not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	The variant was identified in multiple GenomeConnect participants. Variant interpreted as Uncertain significance and reported on 03-29-2018 by Lab or GTR ID Northwell Health Laboratories. Variant interpreted as Uncertain significance and reported, most recently, on 12/04/2018 by GTR ID Credit Valley Hospital Department of Laboratory Medicine. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -
Uncertain significance, criteria provided, single submitter	clinical testing	Quest Diagnostics Nichols Institute San Juan Capistrano	Sep 01, 2023	In the published literature, this variant has been reported in individuals with breast cancer (PMIDs: 36653541 (2023), 35886069 (2022), 33558524 (2021), 33134171 (2020), 31050813 (2019), 29484706 (2018), 29335925 (2018), 28779002 (2017), 25186627 (2015), 24390236 (2014), 21244692 (2011)), endometrial cancer (PMID:27443514 (2016)), colorectal cancer (PMID: 29987844 (2018)), and prostate cancer (PMIDs: 18571837 (2008), 17721994 (2007), 14612911 (2003)). This variant has also been identified in healthy control individuals (PMIDs: 36653541 (2023), 31050813 (2019), 30303537 (2019), 28779002 (2017), 21244692 (2011), 17721994 (2007)), and reported to co-occur with deleterious variants in the MRE11 and MSH2 genes (PMIDs: 33134171 (2020), 27443514 (2016)). Case-control studies suggest this variant is associated with prostate cancer risk but not breast cancer risk (PMIDs: 27595995 (2016), 36653541 (2023)). In addition, experimental studies indicate this variant has neutral to intermediate effects on CHEK2 protein function (PMIDs: 34903604 (2022), 31050813 (2019), 30851065 (2019), 17721994 (2007)). The frequency of this variant in the general population, 0.0013 (32/25122 chromosomes in European (Finnish) subpopulation (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is higher than would generally be expected for pathogenic variants in this gene. Based on the available information, we are unable to determine the clinical significance of this variant. -
Uncertain significance, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Uncertain significance, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Uncertain significance, no assertion criteria provided	clinical testing	Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	-	- -

Familial cancer of breast Uncertain:2 Benign:3

Uncertain significance, criteria provided, single submitter	clinical testing	Counsyl	Aug 12, 2016	- -
Uncertain significance, no assertion criteria provided	research	Center of Medical Genetics and Primary Health Care	Apr 08, 2020	ACMG Guidelines 2015 criteria PM1 Pathogenic Moderate: Pkinase domain (M265-529L aa) which contains the catalytic function of protein kinases. Hot-spot has 21 non-VUS coding variants (7 pathogenic and 14 benign), pathogenicity = 33.3%, proximity score 3.967 > threshold 2.472. PP1 Pathogenic Supporting: Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease. PP2 Pathogenic Supporting: 30 out of 48 non-VUS missense variants in gene CHEK2 are pathogenic = 62.5% > threshold of 51.0%, and 308 out of 1,604 clinically reported variants in gene CHEK2 are pathogenic = 19.2% > threshold of 12.0%. PP1 Pathogenic Supporting: 2 patients are sibs (sisters) who share the same variant. BP4 Benign Supporting: 6 benign predictions from DEOGEN2, EIGEN, MVP, MutationAssessor, PrimateAI and REVEL vs 5 pathogenic predictions from DANN, FATHMM-MKL, M-CAP, MutationTaster and SIFT and the position is not conserved." Therefore, this variant was classified as a Variant of Unknown Significance. -
Likely benign, criteria provided, single submitter	clinical testing	Myriad Genetics, Inc.	Mar 09, 2023	This variant is considered likely benign. This variant is strongly associated with less severe personal and family histories of cancer, typical for individuals without pathogenic variants in this gene [PMID: 25085752]. -
Likely benign, criteria provided, single submitter	research	Research Unit of Translational Medicine, University of Oulu	Nov 22, 2022	The frequency of p.Asp438Tyr variant in CHEK2 among Northern Finnish breast cancer cases was 0.6% (14/2284) and nearly equal in geographically matched healthy population controls (0.8%, 10/1299) in a study by Kumpula et al. (2023). Similar carrier frequencies in the studied cases and the general population argue against association of CHEK2 p.Asp438Tyr with increased breast cancer risk. Therefore the variant can be classified as likely benign. -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Hereditary cancer-predisposing syndrome Uncertain:2 Benign:2

Uncertain significance, criteria provided, single submitter	clinical testing	GeneKor MSA	Aug 01, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	Color Diagnostics, LLC DBA Color Health	Aug 30, 2019	- -
Uncertain significance, criteria provided, single submitter	research	Department of Pediatric Oncology, Hematology and Clinical Immunology, University Clinics Duesseldorf	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Dec 14, 2020	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not specified Uncertain:2 Benign:1

Likely benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Aug 28, 2023	Variant summary: CHEK2 c.1312G>T (p.Asp438Tyr) results in a non-conservative amino acid change located in the Protein kinase domain (IPR000719) 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 0.0004 in 261860 control chromosomes, predominantly at a frequency of 0.00046 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 1.5- fold 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 is a benign polymorphism found primarily in populations of Non-Finnish European origin. However, the frequency in gnomAD and the cases reported in the literature may not be accurate due to the sequencing technology used being unable to distinguish between CHEK2 and its multiple overlapping pseudogenes. This variant has also been reported among 7 women older than 70 years who have never had cancer as reported in the FLOSSIES database. c.1312G>T, has been reported in the literature in individuals affected with Breast and/or Ovarian Cancer, but also in controls and in a family where it did not segregate with disease (examples- Baloch_2013, Bell_2007, LeCalvez-Kelm_2011, Seppala_2003, Tischkowitz_2008, Young_2016, Yadav_2016, Tung_2015, Maxwell_2016, Fostira_2018, Scarpetta_2019). Case control approaches indicated no significant risk association for breast cancer, but a slightly elevated risk for prostate cancer (Le Calvez-Kelm_2011, Southey_2016). These data thus do not allow any conclusion about variant significance. At-least one co-occurrence with another pathogenic variant has been reported (MSH2 c.1697del, p.Asn566IlefsX24), providing supporting evidence for a benign role (Ring_2016). In a mammalian cell based kinase-assay the variant protein showed about 70% reduction in activity (Bell_2007), whereas in a yeast based DNA-damage assay the variant showed similar function to the wild type supporting a benign outcome (Delimitsou_2019). The following publications have been ascertained in the context of this evaluation (PMID: 24390236, 17721994, 15087378, 30851065, 31811167, 29335925, 30303537, 33134171, 29484706, 25231023, 29987844, 21244692, 30322893, 27153395, 33558524, 27443514, 31512090, 14612911, 27595995, 18571837, 31159747, 25186627, 29875428, 27878467, 31214250, 26787654, 28828701, 23960188). Multiple clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and cited the variant as uncertain significance (n=15) and likely benign (n=5). Based on the evidence outlined above, the variant was classified as likely benign. -
Uncertain significance, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Jan 11, 2019	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	Jul 31, 2024	- -

CHEK2-related cancer predisposition Uncertain:1 Other:1

Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
not provided, no classification provided	phenotyping only	GenomeConnect - Invitae Patient Insights Network	-	Variant interpreted as Likely benign and reported on 04-04-2017 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. -

CHEK2-related disorder Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 30, 2024

The CHEK2 c.1312G>T variant is predicted to result in the amino acid substitution p.Asp438Tyr. This variant has been reported in individuals with a history of breast, prostate, and colorectal cancers; but has also been reported in unaffected control individuals (Baloch et al. 2014. PubMed ID: 24390236; Supplementary Table 1, Le Calvez-Kelm et al. 2011. PubMed ID: 21244692; Tischkowitz et al. 2008. PubMed ID: 18571837; Kleiblova et al. 2019. PubMed ID: 31050813; Moradian et al. 2021. PubMed ID: 33558524; Biscaglia et al. 2022. PubMed ID: 34347074). Functional studies have shown this variant impacts CHEK2 kinase activity by 70% when compared to wild-type protein; however, it is unclear whether this is sufficient to contribute to disease (Bell et al. 2007. PubMed ID: 17721994). This variant is reported in 0.13% of alleles in individuals of European (Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/22-29091178-C-A). It has conflicting interpretations in ClinVar ranging from likely benign to uncertain significance (https://www.ncbi.nlm.nih.gov/clinvar/variation/128056/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Breast and/or ovarian cancer Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Feb 27, 2023

- -

Familial cancer of breast;C0376358:Malignant tumor of prostate;C0585442:Bone osteosarcoma;C5882668:Li-Fraumeni syndrome 2 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

May 23, 2017

- -

Hereditary breast ovarian cancer syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

curation

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

Jan 09, 2024

Results from functional assays as well as predictions are contradictory. According to the ACMG standard criteria we chose this criterium: BS1 (strong benign): gnomAD v3.1.2 (non-cancer): AF: 0.0005092 + 1 x hom -

Li-Fraumeni syndrome 2 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Baylor Genetics

Oct 12, 2019

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -

Carcinoma of colon Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Department of Pathology and Laboratory Medicine, Sinai Health System

-

The CHEK2 p.Asp438Tyr variant was identified in 4 of 1332 proband chromosomes (frequency: 0.003) from Pakistani, Finnish, Polish and Ashkenazi Jewish individuals or families with breast, early onset breast and prostate, or hereditary prostate cancer and was not identified in 590 control chromosomes from healthy individuals (Baloch 2014, Seppala 2003, Tischkowitz 2008, Bell 2007). The variant was identified in dbSNP (ID: rs200050883) “With Uncertain significance allele”, ClinVar (classified as uncertain significance by GeneDx, Ambry Genetics, Invitae, Counsyl, and Color Genomics), and the Zhejiang Colon Cancer Database (14x, co-occurring with CHEK2 c.1100delC). The variant was not identified in Cosmic. The variant was identified in control databases in 108 of 276806 chromosomes at a frequency of 0.0004 (Genome Aggregation Consortium Feb 27, 2017). The variant was identified in the following populations: European in 57 of 126326 chromosomes (frequency: 0.0005), Finnish in 33 of 25792 chromosomes (frequency: 0.001), African in 3 of 24032 chromosomes (frequency: 0.0001), Other in 4 of 6456 chromosomes (frequency: 0.0006), Latino in 2 of 34404 chromosomes (frequency: 0.00006), and South Asian in 9 of 30776 chromosomes (frequency: 0.0003). The variant occurs in the catalytic domain of the CHEK2 protein and in vitro analysis of kinase activity showed the variant had a 70% decrease in activity compared to wildtype (Baloch 2014, Bell 2007). The p.Asp438 residue is conserved in mammals but not in more distantly related organisms, and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the Tyr variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. -

Hereditary cancer Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Mendelics

Jan 23, 2024

- -

Malignant tumor of breast Benign:1

Likely benign, no assertion criteria provided

clinical testing

Center of Medical Genetics and Primary Health Care

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Uncertain	-0.010
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T;.;T;.;T;.;T;.;.
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.97	D
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.046	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.3	L;.;L;.;L;.;L;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-4.9	D;D;D;.;D;D;.;D;D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0020	D;D;D;.;D;D;.;D;D
Sift4G	Uncertain	0.0070	D;D;D;.;D;D;.;D;D
Polyphen		1.0	D;D;D;.;D;P;D;D;D
Vest4		0.74
MVP		0.83
MPC		0.15
ClinPred		0.16	T
GERP RS		5.8
Varity_R		0.82
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs200050883; hg19: chr22-29091178; COSMIC: COSV105248010; COSMIC: COSV105248010;