2-47488805-C-T

Position:

• chr2-47488805-C-T

Variant summary

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

The NM_001406674.1(MSH2):​c.2634+7934C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 151,970 control chromosomes in the GnomAD database, including 11,488 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 0.37 (11488 hom., cov: 32)
• Consequence: MSH2 NM_001406674.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66

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=-0.67).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSH2	NM_001406674.1	c.2634+7934C>T		intron_variant			NP_001393603.1
MSH2	NM_001406631.1	c.2634+7934C>T		intron_variant			NP_001393560.1
MSH2	NM_001406632.1	c.2634+7934C>T		intron_variant			NP_001393561.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSH2	ENST00000406134.5	c.2634+7934C>T		intron_variant		1		ENSP00000384199.1
MSH2	ENST00000645506.1	c.2634+7934C>T		intron_variant				ENSP00000495455.1
MSH2	ENST00000644092.1	n.*934+7934C>T		intron_variant				ENSP00000496351.1

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56080 AN: 151852 Hom.: 11473 Cov.: 32

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.661

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.337

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

GnomAD4 genome AF: 0.369 AC: 56147 AN: 151970 Hom.: 11488 Cov.: 32 AF XY: 0.374 AC XY: 27771 AN XY: 74278

Gnomad4 AFR AF: 0.509

Gnomad4 AMR AF: 0.342

Gnomad4 ASJ AF: 0.229

Gnomad4 EAS AF: 0.659

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.395

Gnomad4 NFE AF: 0.277

Gnomad4 OTH AF: 0.336

Alfa AF: 0.291 Hom.: 8900

Bravo AF: 0.370

Asia WGS AF: 0.502 AC: 1743 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.84
DANN	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6544992; hg19: chr2-47715944;