rs7355698

Positions:

• chr2-47486535-T-G

Variant summary

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

The NM_001406674.1(MSH2):​c.2634+5664T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0327 in 152,278 control chromosomes in the GnomAD database, including 133 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 0.033 (133 hom., cov: 33)
• Consequence: MSH2 NM_001406674.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.497

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=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSH2	NM_001406674.1	c.2634+5664T>G		intron_variant			NP_001393603.1
MSH2	NM_001406631.1	c.2634+5664T>G		intron_variant			NP_001393560.1
MSH2	NM_001406632.1	c.2634+5664T>G		intron_variant			NP_001393561.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSH2	ENST00000406134.5	c.2634+5664T>G		intron_variant		1		ENSP00000384199.1
MSH2	ENST00000645506.1	c.2634+5664T>G		intron_variant				ENSP00000495455.1
MSH2	ENST00000644092.1	n.*934+5664T>G		intron_variant				ENSP00000496351.1

Frequencies

GnomAD3 genomes AF: 0.0326 AC: 4968 AN: 152160 Hom.: 132 Cov.: 33

Gnomad AFR AF: 0.0652

Gnomad AMI AF: 0.00769

Gnomad AMR AF: 0.0184

Gnomad ASJ AF: 0.0366

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0344

Gnomad FIN AF: 0.0147

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0212

Gnomad OTH AF: 0.0335

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

GnomAD4 genome AF: 0.0327 AC: 4972 AN: 152278 Hom.: 133 Cov.: 33 AF XY: 0.0313 AC XY: 2332 AN XY: 74452

Gnomad4 AFR AF: 0.0652

Gnomad4 AMR AF: 0.0183

Gnomad4 ASJ AF: 0.0366

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0342

Gnomad4 FIN AF: 0.0147

Gnomad4 NFE AF: 0.0212

Gnomad4 OTH AF: 0.0331

Alfa AF: 0.0331 Hom.: 16

Bravo AF: 0.0335

Asia WGS AF: 0.0240 AC: 84 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	11
DANN	Benign	0.89

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7355698; hg19: chr2-47713674;