Variant 7-6004166-C-G 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 ENST00000265849.12(PMS2):c.164-108G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0752 in 698,068 control chromosomes in the GnomAD database, including 4,223 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.057 ( 559 hom., cov: 32)

Exomes 𝑓: 0.080 ( 3664 hom. )

Consequence

PMS2
ENST00000265849.12 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.243

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=-0.82).

BP6

Variant 7-6004166-C-G is Benign according to our data. Variant chr7-6004166-C-G is described in ClinVar as [Benign]. Clinvar id is 490096.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-6004166-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PMS2	NM_000535.7 linkuse as main transcript	c.164-108G>C		intron_variant		ENST00000265849.12	NP_000526.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PMS2	ENST00000265849.12 linkuse as main transcript	c.164-108G>C		intron_variant		1	NM_000535.7	ENSP00000265849	P3	P54278-1

Frequencies

GnomAD3 genomes

AF:

0.0567

AC:

8615

AN:

152016

Hom.:

558

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0215

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0630

Gnomad ASJ

AF:

0.0629

Gnomad EAS

AF:

0.342

Gnomad SAS

AF:

0.161

Gnomad FIN

AF:

0.0947

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0419

Gnomad OTH

AF:

0.0550

GnomAD4 exome

AF:

0.0803

AC:

43843

AN:

545934

Hom.:

3664

Cov.:

AF XY:

0.0827

AC XY:

24534

AN XY:

296644

show subpopulations

Gnomad4 AFR exome

AF:

0.0198

Gnomad4 AMR exome

AF:

0.0793

Gnomad4 ASJ exome

AF:

0.0656

Gnomad4 EAS exome

AF:

0.358

Gnomad4 SAS exome

AF:

0.150

Gnomad4 FIN exome

AF:

0.0938

Gnomad4 NFE exome

AF:

0.0427

Gnomad4 OTH exome

AF:

0.0731

GnomAD4 genome

AF:

0.0567

AC:

8622

AN:

152134

Hom.:

559

Cov.:

AF XY:

0.0615

AC XY:

4572

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.0216

Gnomad4 AMR

AF:

0.0627

Gnomad4 ASJ

AF:

0.0629

Gnomad4 EAS

AF:

0.342

Gnomad4 SAS

AF:

0.161

Gnomad4 FIN

AF:

0.0947

Gnomad4 NFE

AF:

0.0419

Gnomad4 OTH

AF:

0.0610

Alfa

AF:

0.0191

Hom.:

Bravo

AF:

0.0520

Asia WGS

AF:

0.246

AC:

854

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary nonpolyposis colorectal neoplasms

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 15, 2024

- -

Hereditary cancer-predisposing syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Color Diagnostics, LLC DBA Color Health

Dec 10, 2014

- -

Lynch syndrome 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Counsyl

Sep 06, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.98

DANN

Benign

0.47

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