Variant 7-5995876-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000535.7(PMS2):c.804-243G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,128 control chromosomes in the GnomAD database, including 2,139 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).

Frequency

Genomes: 𝑓 0.16 ( 2139 hom., cov: 32)

Consequence

PMS2
NM_000535.7 intron

Scores

Clinical Significance

Benign reviewed by expert panel B:1

Conservation

PhyloP100: 0.292

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 7-5995876-C-T is Benign according to our data. Variant chr7-5995876-C-T is described in ClinVar as [Benign]. Clinvar id is 91371.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-5995876-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PMS2	NM_000535.7 linkuse as main transcript	c.804-243G>A		intron_variant		ENST00000265849.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PMS2	ENST00000265849.12 linkuse as main transcript	c.804-243G>A		intron_variant		1	NM_000535.7	P3	P54278-1

Frequencies

GnomAD3 genomes

AF:

0.159

AC:

24116

AN:

152010

Hom.:

2133

Cov.:

show subpopulations

Gnomad AFR

AF:

0.215

Gnomad AMI

AF:

0.188

Gnomad AMR

AF:

0.106

Gnomad ASJ

AF:

0.207

Gnomad EAS

AF:

0.0669

Gnomad SAS

AF:

0.148

Gnomad FIN

AF:

0.175

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.139

Gnomad OTH

AF:

0.153

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.159

AC:

24123

AN:

152128

Hom.:

2139

Cov.:

AF XY:

0.160

AC XY:

11882

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.215

Gnomad4 AMR

AF:

0.105

Gnomad4 ASJ

AF:

0.207

Gnomad4 EAS

AF:

0.0661

Gnomad4 SAS

AF:

0.147

Gnomad4 FIN

AF:

0.175

Gnomad4 NFE

AF:

0.139

Gnomad4 OTH

AF:

0.151

Alfa

AF:

0.140

Hom.:

3094

Bravo

AF:

0.155

Asia WGS

AF:

0.113

AC:

394

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

Lynch syndrome

Benign:1

Benign, reviewed by expert panel

research

International Society for Gastrointestinal Hereditary Tumours (InSiGHT)

Sep 05, 2013

MAF >1% -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.1

DANN

Benign

0.54

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over