2-47448192-G-C

Position:

• chr2-47448192-G-C

Variant summary

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

The NM_000251.3(MSH2):​c.1386+2535G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 152,056 control chromosomes in the GnomAD database, including 23,481 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 0.53 (23481 hom., cov: 32)
• Consequence: MSH2 NM_000251.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.883

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.775 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSH2	NM_000251.3	c.1386+2535G>C		intron_variant		ENST00000233146.7	NP_000242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSH2	ENST00000233146.7	c.1386+2535G>C		intron_variant		1	NM_000251.3	ENSP00000233146.2

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80229 AN: 151938 Hom.: 23436 Cov.: 32

Gnomad AFR AF: 0.782

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.530

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.488

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

GnomAD4 genome AF: 0.528 AC: 80333 AN: 152056 Hom.: 23481 Cov.: 32 AF XY: 0.531 AC XY: 39448 AN XY: 74326

Gnomad4 AFR AF: 0.783

Gnomad4 AMR AF: 0.418

Gnomad4 ASJ AF: 0.371

Gnomad4 EAS AF: 0.676

Gnomad4 SAS AF: 0.467

Gnomad4 FIN AF: 0.530

Gnomad4 NFE AF: 0.400

Gnomad4 OTH AF: 0.488

Alfa AF: 0.482 Hom.: 2372

Bravo AF: 0.529

Asia WGS AF: 0.577 AC: 2008 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.63
DANN	Benign	0.25

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: rs3771275; hg19: chr2-47675331;