rs182017009

Positions:

• chr2-47678259-C-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001406633.1(MSH2):​c.2905C>A​(p.His969Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000731 in 456,652 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 4/4 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.00068 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00076 (1 hom.)
• Consequence: MSH2 NM_001406633.1 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.434

Genes affected

MSH2 (HGNC:7325): (mutS homolog 2) This locus is frequently mutated in hereditary nonpolyposis colon cancer (HNPCC). When cloned, it was discovered to be a human homolog of the E. coli mismatch repair gene mutS, consistent with the characteristic alterations in microsatellite sequences (RER+ phenotype) found in HNPCC. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

MSH2 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSH2	NM_001406633.1	c.2905C>A	p.His969Asn	missense_variant	18/19		NP_001393562.1
MSH2	NM_001406637.1	c.2753-29924C>A		intron_variant			NP_001393566.1
MSH2	NR_176241.1	n.3107C>A		non_coding_transcript_exon_variant	20/21

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.000684 AC: 104 AN: 152130 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00226

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00104

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000535 AC: 72 AN: 134586 Hom.: 0 AF XY: 0.000518 AC XY: 38 AN XY: 73296

Gnomad AFR exome AF: 0.000155

Gnomad AMR exome AF: 0.0000409

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00241

Gnomad NFE exome AF: 0.00100

Gnomad OTH exome AF: 0.000965

GnomAD4 exome AF: 0.000756 AC: 230 AN: 304404 Hom.: 1 Cov.: 0 AF XY: 0.000698 AC XY: 121 AN XY: 173340

Gnomad4 AFR exome AF: 0.000348

Gnomad4 AMR exome AF: 0.0000367

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00289

Gnomad4 NFE exome AF: 0.00114

Gnomad4 OTH exome AF: 0.000562

GnomAD4 genome AF: 0.000683 AC: 104 AN: 152248 Hom.: 0 Cov.: 31 AF XY: 0.000631 AC XY: 47 AN XY: 74448

Gnomad4 AFR AF: 0.000144

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00226

Gnomad4 NFE AF: 0.00104

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00100 Hom.: 0

Bravo AF: 0.000555

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not specified Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs182017009; hg19: chr2-47905398;