2-47782786-G-A

Position:

• chr2-47782786-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000652107.1(MSH6):​c.-37-8141G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0914 in 152,196 control chromosomes in the GnomAD database, including 717 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).

• Frequency: Genomes: 𝑓 0.091 (717 hom., cov: 33)
• Consequence: MSH6 ENST00000652107.1 intron
• Clinical Significance: Benign reviewed by expert panel B:2
• Conservation: PhyloP100: 0.124

Genes affected

MSH6 (HGNC:7329): (mutS homolog 6) This gene encodes a member of the DNA mismatch repair MutS family. In E. coli, the MutS protein helps in the recognition of mismatched nucleotides prior to their repair. A highly conserved region of approximately 150 aa, called the Walker-A adenine nucleotide binding motif, exists in MutS homologs. The encoded protein heterodimerizes with MSH2 to form a mismatch recognition complex that functions as a bidirectional molecular switch that exchanges ADP and ATP as DNA mismatches are bound and dissociated. Mutations in this gene may be associated with hereditary nonpolyposis colon cancer, colorectal cancer, and endometrial cancer. Transcripts variants encoding different isoforms have been described. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-47782786-G-A is Benign according to our data. Variant chr2-47782786-G-A is described in ClinVar as [Benign]. Clinvar id is 89162.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47782786-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSH6	ENST00000652107.1	c.-37-8141G>A		intron_variant				ENSP00000498629

Frequencies

GnomAD3 genomes AF: 0.0914 AC: 13893 AN: 152076 Hom.: 715 Cov.: 33

Gnomad AFR AF: 0.0825

Gnomad AMI AF: 0.0451

Gnomad AMR AF: 0.0603

Gnomad ASJ AF: 0.0366

Gnomad EAS AF: 0.000773

Gnomad SAS AF: 0.0180

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.0904

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

GnomAD4 genome AF: 0.0914 AC: 13916 AN: 152196 Hom.: 717 Cov.: 33 AF XY: 0.0904 AC XY: 6727 AN XY: 74416

Gnomad4 AFR AF: 0.0828

Gnomad4 AMR AF: 0.0602

Gnomad4 ASJ AF: 0.0366

Gnomad4 EAS AF: 0.000775

Gnomad4 SAS AF: 0.0184

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.0890

Alfa AF: 0.103 Hom.: 101

Bravo AF: 0.0837

Asia WGS AF: 0.0170 AC: 59 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: reviewed by expert panel

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% -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.2
DANN	Benign	0.90

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3136229; hg19: chr2-48009925;