chr7-5987027-T-A

Variant names:

• chr7-5987027-T-A
• rs267608169
• NM_000535.7:c.1738A>T

Variant summary

Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1 PM2 PP5_Very_Strong

The NM_000535.7(PMS2):​c.1738A>T​(p.Lys580*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★★). Synonymous variant affecting the same amino acid position (i.e. K580K) has been classified as Benign. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PMS2 NM_000535.7 stop_gained
• Clinical Significance: Pathogenic reviewed by expert panel P:10
• Conservation: PhyloP100: 4.72
• Publications: 18 publications found

Genes affected

PMS2 (HGNC:9122): (PMS1 homolog 2, mismatch repair system component) The protein encoded by this gene is a key component of the mismatch repair system that functions to correct DNA mismatches and small insertions and deletions that can occur during DNA replication and homologous recombination. This protein forms heterodimers with the gene product of the mutL homolog 1 (MLH1) gene to form the MutL-alpha heterodimer. The MutL-alpha heterodimer possesses an endonucleolytic activity that is activated following recognition of mismatches and insertion/deletion loops by the MutS-alpha and MutS-beta heterodimers, and is necessary for removal of the mismatched DNA. There is a DQHA(X)2E(X)4E motif found at the C-terminus of the protein encoded by this gene that forms part of the active site of the nuclease. Mutations in this gene have been associated with hereditary nonpolyposis colorectal cancer (HNPCC; also known as Lynch syndrome) and Turcot syndrome. [provided by RefSeq, Apr 2016]

PMS2 Gene-Disease associations (from GenCC):

• Lynch syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• Lynch syndrome 4

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• mismatch repair cancer syndrome 1

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• mismatch repair cancer syndrome 4

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• malignant pancreatic neoplasm

  Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
• ovarian cancer

  Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
• Muir-Torre syndrome

  Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
• rhabdomyosarcoma

  Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
• breast cancer

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• prostate cancer

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• hereditary breast carcinoma

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Pathogenic. The variant received 18 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 7-5987027-T-A is Pathogenic according to our data. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5987027-T-A is described in CliVar as Pathogenic. Clinvar id is 91312.Status of the report is reviewed_by_expert_panel, 3 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PMS2	NM_000535.7	c.1738A>T	p.Lys580*	stop_gained	Exon 11 of 15	ENST00000265849.12	NP_000526.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PMS2	ENST00000265849.12	c.1738A>T	p.Lys580*	stop_gained	Exon 11 of 15	1	NM_000535.7	ENSP00000265849.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:10

Revision: reviewed by expert panel

Submissions by phenotype

Lynch syndrome 4 Pathogenic:3

Jul 22, 2021

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 22, 2023

Baylor Genetics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 20, 2023

Myriad Genetics, Inc.

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. -

Lynch syndrome Pathogenic:2

Sep 05, 2013

International Society for Gastrointestinal Hereditary Tumours (InSiGHT)

Significance: Pathogenic

Review Status: reviewed by expert panel

Collection Method: research

Coding sequence variation resulting in a stop codon -

Sep 23, 2024

All of Us Research Program, National Institutes of Health

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant changes 1 nucleotide in exon 11 of the PMS2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with MMR-deficient colorectal cancer (PMID: 18602922, 26895986). This variant also has been detected in at least two individuals affected with constitutional mismatch repair deficiency syndrome as a homozygous mutation and as a heterozygous mutation in trans with a PMS2 truncation variant (PMID: 31433215, 32642664, 33259954). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of PMS2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. -

Hereditary cancer-predisposing syndrome Pathogenic:2

Oct 10, 2023

Ambry Genetics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The p.K580* pathogenic mutation (also known as c.1738A>T), located in coding exon 11 of the PMS2 gene, results from an A to T substitution at nucleotide position 1738. This changes the amino acid from a lysine to a stop codon within coding exon 11. This mutation was detected in a patient diagnosed with cancer of the transverse colon at age 49, whose tumor showed isolated loss of PMS2 protein on IHC (Senter L et al. Gastroenterology. 2008 Aug;135(2):419-28). In addition, this mutation was observed along with another truncating PMS2 mutation in a patient with congenital mismatch repair deficiency syndrome who was diagnosed with high grade glioma at age 7 and lymphoblastic lymphoma at age 9 (Guerrini-Rousseau L et al. Neurooncol. Adv. 2019 Dec;1(1):vdz033). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. -

Feb 21, 2024

Color Diagnostics, LLC DBA Color Health

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant changes 1 nucleotide in exon 11 of the PMS2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in multiple individuals affected with Lynch syndrome-associated cancers (PMID: 18602922, 26895986, 31992580, 34285288). This variant also has been detected in individuals affected with constitutional mismatch repair deficiency syndrome as a homozygous mutation or as a heterozygous mutation in trans with a PMS2 truncation variant (PMID: 31433215, 32642664, 33259954). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of PMS2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. -

Hereditary nonpolyposis colon cancer Pathogenic:1

Oct 10, 2022

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

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: PMS2 c.1738A>T (p.Lys580X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251348 control chromosomes (gnomAD). c.1738A>T has been reported in the literature in multiple individuals affected with colorectal cancer, including cases where the tumor was confirmed to have high microsatellite instability (MSI-H) and/or absent PMS2 by immunohistochemistry (e.g. Senter_2008, Epenschied_2017, Gong_2019, Wang_2020) and in a compound heterozygous individual with constitutional mismatch repair deficiency (Okkels_2019). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. -

not provided Pathogenic:1

Nov 27, 2024

GeneDx

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; This variant is associated with the following publications: (PMID: 28454591, 28514183, 18602922, 26895986, 25691505, 14574005, 31118792, 30787465, 34178123, 32719484, 28888541, 31992580, 32782288, 35273153, 31830689, 31433215, 32642664, 33259954, 37310942) -

Hereditary nonpolyposis colorectal neoplasms Pathogenic:1

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change creates a premature translational stop signal (p.Lys580*) in the PMS2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PMS2 are known to be pathogenic (PMID: 21376568, 24362816). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with colon cancer (PMID: 18602922). Invitae Evidence Modeling of clinical and family history, age, sex, and reported ancestry of multiple individuals with this PMS2 variant has been performed. This variant is expected to be pathogenic with a positive predictive value of at least 99%. This is a validated machine learning model that incorporates the clinical features of 1,370,736 individuals referred to our laboratory for PMS2 testing. ClinVar contains an entry for this variant (Variation ID: 91312). For these reasons, this variant has been classified as Pathogenic. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.50	D
BayesDel_noAF	Pathogenic	0.48
CADD	Pathogenic	36
DANN	Uncertain	0.99
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.96	D
PhyloP100		4.7
Vest4		0.89
GERP RS		5.8
Mutation Taster		=0/200	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs267608169; hg19: chr7-6026658;