Variant rs3815383 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.903+84C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0738 in 836,554 control chromosomes in the GnomAD database, including 4,767 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.057 ( 573 hom., cov: 32)

Exomes 𝑓: 0.078 ( 4194 hom. )

Consequence

PMS2
ENST00000265849.12 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0480

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=-0.79).

BP6

Variant 7-5995450-G-A is Benign according to our data. Variant chr7-5995450-G-A is described in ClinVar as [Benign]. Clinvar id is 596289.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-5995450-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.335 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.903+84C>T		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.903+84C>T		intron_variant		1	NM_000535.7	ENSP00000265849	P3	P54278-1

Frequencies

GnomAD3 genomes

AF:

0.0565

AC:

8597

AN:

152112

Hom.:

572

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0211

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0623

Gnomad ASJ

AF:

0.0628

Gnomad EAS

AF:

0.348

Gnomad SAS

AF:

0.159

Gnomad FIN

AF:

0.0942

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0418

Gnomad OTH

AF:

0.0531

GnomAD4 exome

AF:

0.0777

AC:

53171

AN:

684324

Hom.:

4194

AF XY:

0.0803

AC XY:

29563

AN XY:

368242

show subpopulations

Gnomad4 AFR exome

AF:

0.0189

Gnomad4 AMR exome

AF:

0.0859

Gnomad4 ASJ exome

AF:

0.0654

Gnomad4 EAS exome

AF:

0.362

Gnomad4 SAS exome

AF:

0.148

Gnomad4 FIN exome

AF:

0.0934

Gnomad4 NFE exome

AF:

0.0430

Gnomad4 OTH exome

AF:

0.0731

GnomAD4 genome

AF:

0.0565

AC:

8601

AN:

152230

Hom.:

573

Cov.:

AF XY:

0.0613

AC XY:

4566

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0211

Gnomad4 AMR

AF:

0.0621

Gnomad4 ASJ

AF:

0.0628

Gnomad4 EAS

AF:

0.348

Gnomad4 SAS

AF:

0.159

Gnomad4 FIN

AF:

0.0942

Gnomad4 NFE

AF:

0.0418

Gnomad4 OTH

AF:

0.0591

Alfa

AF:

0.0464

Hom.:

Bravo

AF:

0.0521

Asia WGS

AF:

0.244

AC:

845

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Mar 19, 2018

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

This variant is associated with the following publications: (PMID: 28874130) -

Hereditary nonpolyposis colorectal neoplasms

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 15, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.1

DANN

Benign

0.80

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