chr2-47678251-C-A

Position:

• chr2-47678251-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001406633.1(MSH2):​c.2897C>A​(p.Pro966His) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0391 in 456,450 control chromosomes in the GnomAD database, including 965 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 0.035 (275 hom., cov: 32)
  • Exomes 𝑓: 0.041 (690 hom.)
• Consequence: MSH2 NM_001406633.1 missense, splice_region
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.295

Genes affected

MSH2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSH2	NM_001406633.1	c.2897C>A	p.Pro966His	missense_variant, splice_region_variant	18/19		NP_001393562.1
MSH2	NM_001406637.1	c.2753-29932C>A		intron_variant			NP_001393566.1
MSH2	NR_176241.1	n.3099C>A		splice_region_variant, non_coding_transcript_exon_variant	20/21

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0354 AC: 5383 AN: 152030 Hom.: 274 Cov.: 32

Gnomad AFR AF: 0.00645

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0510

Gnomad ASJ AF: 0.0704

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.0427

Gnomad FIN AF: 0.0439

Gnomad MID AF: 0.0478

Gnomad NFE AF: 0.0256

Gnomad OTH AF: 0.0468

GnomAD3 exomes AF: 0.0573 AC: 7707 AN: 134504 Hom.: 636 AF XY: 0.0543 AC XY: 3977 AN XY: 73250

Gnomad AFR exome AF: 0.00419

Gnomad AMR exome AF: 0.0573

Gnomad ASJ exome AF: 0.0606

Gnomad EAS exome AF: 0.316

Gnomad SAS exome AF: 0.0306

Gnomad FIN exome AF: 0.0407

Gnomad NFE exome AF: 0.0259

Gnomad OTH exome AF: 0.0466

GnomAD4 exome AF: 0.0409 AC: 12455 AN: 304302 Hom.: 690 Cov.: 0 AF XY: 0.0402 AC XY: 6968 AN XY: 173286

Gnomad4 AFR exome AF: 0.00464

Gnomad4 AMR exome AF: 0.0559

Gnomad4 ASJ exome AF: 0.0612

Gnomad4 EAS exome AF: 0.314

Gnomad4 SAS exome AF: 0.0321

Gnomad4 FIN exome AF: 0.0421

Gnomad4 NFE exome AF: 0.0260

Gnomad4 OTH exome AF: 0.0443

GnomAD4 genome AF: 0.0354 AC: 5383 AN: 152148 Hom.: 275 Cov.: 32 AF XY: 0.0381 AC XY: 2836 AN XY: 74390

Gnomad4 AFR AF: 0.00643

Gnomad4 AMR AF: 0.0511

Gnomad4 ASJ AF: 0.0704

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.0423

Gnomad4 FIN AF: 0.0439

Gnomad4 NFE AF: 0.0256

Gnomad4 OTH AF: 0.0463

Alfa AF: 0.0251 Hom.: 29

Bravo AF: 0.0379

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	-0.91
CADD	Benign	0.69
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17036817; hg19: chr2-47905390;