rs17568951

Positions:

• chr2-47580354-T-C

Variant summary

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

The NM_001406631.1(MSH2):​c.2752+67934T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 151,582 control chromosomes in the GnomAD database, including 2,846 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 0.19 (2846 hom., cov: 30)
• Consequence: MSH2 NM_001406631.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98

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 (NFE) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSH2	NM_001406631.1	c.2752+67934T>C		intron_variant			NP_001393560.1
MSH2	NM_001406632.1	c.2752+67934T>C		intron_variant			NP_001393561.1
MSH2	NM_001406633.1	c.2752+67934T>C		intron_variant			NP_001393562.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSH2	ENST00000644092.1	c.*1053-27038T>C		intron_variant, NMD_transcript_variant				ENSP00000496351
MSH2	ENST00000645339.1	c.2753-52448T>C		intron_variant, NMD_transcript_variant				ENSP00000496441
MSH2	ENST00000646415.1	c.2753-27038T>C		intron_variant, NMD_transcript_variant				ENSP00000495543

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28074 AN: 151464 Hom.: 2847 Cov.: 30

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.00482

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.185 AC: 28066 AN: 151582 Hom.: 2846 Cov.: 30 AF XY: 0.182 AC XY: 13485 AN XY: 74012

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.00502

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.235

Gnomad4 OTH AF: 0.183

Alfa AF: 0.215 Hom.: 1472

Bravo AF: 0.183

Asia WGS AF: 0.0800 AC: 280 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.039
DANN	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17568951; hg19: chr2-47807493;