rs12999145

chr2-47459547-A-Gchr2-47459547-A-T

Variant summary

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

The NM_000251.3(MSH2):c.1387-3484A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0991 in 151,144 control chromosomes in the GnomAD database, including 1,349 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.099 (1349 hom., cov: 32)
• Consequence: MSH2 NM_000251.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.815

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSH2	NM_000251.3	c.1387-3484A>G		intron_variant		ENST00000233146.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSH2	ENST00000233146.7	c.1387-3484A>G		intron_variant		1	NM_000251.3	P1

Frequencies

GnomAD3 genomes AF: 0.0992 AC: 14981 AN: 151056 Hom.: 1354 Cov.: 32

Gnomad AFR AF: 0.0256

Gnomad AMI AF: 0.0253

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.0918

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.0992

Gnomad MID AF: 0.0545

Gnomad NFE AF: 0.0986

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.0991 AC: 14971 AN: 151144 Hom.: 1349 Cov.: 32 AF XY: 0.104 AC XY: 7694 AN XY: 73804

Gnomad4 AFR AF: 0.0256

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.0918

Gnomad4 EAS AF: 0.483

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.0992

Gnomad4 NFE AF: 0.0986

Gnomad4 OTH AF: 0.102

Alfa AF: 0.0303 Hom.: 28

Bravo AF: 0.100

Asia WGS AF: 0.272 AC: 944 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	4.7
Dann	Benign	0.90

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

Other links and lift over

dbSNP: rs12999145; hg19: chr2-47686686;