2-47617366-A-G

Position:

• chr2-47617366-A-G

Variant summary

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

The NM_001406631.1(MSH2):​c.2753-43607A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 151,972 control chromosomes in the GnomAD database, including 26,261 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 0.58 (26261 hom., cov: 31)
• Consequence: MSH2 NM_001406631.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.701

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSH2	NM_001406631.1	c.2753-43607A>G		intron_variant
MSH2	NM_001406632.1	c.2753-39834A>G		intron_variant
MSH2	NM_001406633.1	c.2753-43607A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSH2	ENST00000644092.1	c.*1242+9785A>G		intron_variant, NMD_transcript_variant
MSH2	ENST00000645339.1	c.2753-15436A>G		intron_variant, NMD_transcript_variant
MSH2	ENST00000646415.1	c.*125+9785A>G		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87619 AN: 151854 Hom.: 26224 Cov.: 31

Gnomad AFR AF: 0.738

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.471

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.553

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

GnomAD4 genome AF: 0.577 AC: 87697 AN: 151972 Hom.: 26261 Cov.: 31 AF XY: 0.576 AC XY: 42789 AN XY: 74266

Gnomad4 AFR AF: 0.739

Gnomad4 AMR AF: 0.563

Gnomad4 ASJ AF: 0.589

Gnomad4 EAS AF: 0.379

Gnomad4 SAS AF: 0.525

Gnomad4 FIN AF: 0.553

Gnomad4 NFE AF: 0.507

Gnomad4 OTH AF: 0.548

Alfa AF: 0.510 Hom.: 40724

Bravo AF: 0.585

Asia WGS AF: 0.471 AC: 1639 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.15
DANN	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6544997; hg19: chr2-47844505;