Variant 7-6009173-G-C 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 variant allele was found at a frequency of 0.139 in 1,291,306 control chromosomes in the GnomAD database, including 13,694 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).

Frequency

Genomes: 𝑓 0.16 ( 2217 hom., cov: 32)

Exomes 𝑓: 0.14 ( 11477 hom. )

Consequence

intergenic_region

Scores

Clinical Significance

Benign reviewed by expert panel B:1

Conservation

PhyloP100: 0.140

Variant links:

Genes affected

(HGNC:):

links:

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=-0.59).

BP6

Variant 7-6009173-G-C is Benign according to our data. Variant chr7-6009173-G-C is described in ClinVar as [Benign]. Clinvar id is 91280.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-6009173-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
	use as main transcript	n.6009173G>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	Effect	Protein	UniProt
PMS2	ENST00000699820.1 linkuse as main transcript	n.-154C>G	upstream_gene_variant	ENSP00000514621.1	A0A8V8TP55
PMS2	ENST00000699828.1 linkuse as main transcript	n.-154C>G	upstream_gene_variant	ENSP00000514629.1	A0A8V8TQM5
PMS2	ENST00000699830.1 linkuse as main transcript	n.-154C>G	upstream_gene_variant	ENSP00000514631.1	A0A8V8TP66

Frequencies

GnomAD3 genomes

AF:

0.162

AC:

24671

AN:

151986

Hom.:

2212

Cov.:

show subpopulations

Gnomad AFR

AF:

0.229

Gnomad AMI

AF:

0.188

Gnomad AMR

AF:

0.108

Gnomad ASJ

AF:

0.207

Gnomad EAS

AF:

0.0662

Gnomad SAS

AF:

0.145

Gnomad FIN

AF:

0.175

Gnomad MID

AF:

0.169

Gnomad NFE

AF:

0.138

Gnomad OTH

AF:

0.153

GnomAD4 exome

AF:

0.136

AC:

155035

AN:

1139200

Hom.:

11477

Cov.:

AF XY:

0.137

AC XY:

79051

AN XY:

578990

show subpopulations

Gnomad4 AFR exome

AF:

0.223

Gnomad4 AMR exome

AF:

0.0915

Gnomad4 ASJ exome

AF:

0.184

Gnomad4 EAS exome

AF:

0.0755

Gnomad4 SAS exome

AF:

0.149

Gnomad4 FIN exome

AF:

0.174

Gnomad4 NFE exome

AF:

0.133

Gnomad4 OTH exome

AF:

0.140

GnomAD4 genome

AF:

0.162

AC:

24679

AN:

152106

Hom.:

2217

Cov.:

AF XY:

0.163

AC XY:

12120

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.229

Gnomad4 AMR

AF:

0.108

Gnomad4 ASJ

AF:

0.207

Gnomad4 EAS

AF:

0.0656

Gnomad4 SAS

AF:

0.144

Gnomad4 FIN

AF:

0.175

Gnomad4 NFE

AF:

0.138

Gnomad4 OTH

AF:

0.151

Alfa

AF:

0.0440

Hom.:

Bravo

AF:

0.161

Asia WGS

AF:

0.111

AC:

386

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

-0.59

CADD

Benign

6.8

DANN

Benign

0.77

Splicing

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