2-47473818-C-T

Position:

• chr2-47473818-C-T

Variant summary

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

The ENST00000233146.7(MSH2):​c.1760-1207C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 147,096 control chromosomes in the GnomAD database, including 18,476 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 0.49 (18476 hom., cov: 29)
• Consequence: MSH2 ENST00000233146.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.786

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSH2	NM_000251.3	c.1760-1207C>T		intron_variant		ENST00000233146.7	NP_000242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSH2	ENST00000233146.7	c.1760-1207C>T		intron_variant		1	NM_000251.3	ENSP00000233146	P1

Frequencies

GnomAD3 genomes AF: 0.488 AC: 71675 AN: 146994 Hom.: 18451 Cov.: 29

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.528

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.680

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.447

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

GnomAD4 genome AF: 0.488 AC: 71757 AN: 147096 Hom.: 18476 Cov.: 29 AF XY: 0.492 AC XY: 35152 AN XY: 71470

Gnomad4 AFR AF: 0.668

Gnomad4 AMR AF: 0.406

Gnomad4 ASJ AF: 0.346

Gnomad4 EAS AF: 0.679

Gnomad4 SAS AF: 0.448

Gnomad4 FIN AF: 0.532

Gnomad4 NFE AF: 0.385

Gnomad4 OTH AF: 0.449

Alfa AF: 0.382 Hom.: 10455

Bravo AF: 0.476

Asia WGS AF: 0.544 AC: 1889 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.20
DANN	Benign	0.24

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: rs3821227; hg19: chr2-47700957;