2-47418110-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_000251.3(MSH2):c.1076+1681G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 152,044 control chromosomes in the GnomAD database, including 26,894 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency: Genomes: 𝑓 0.57 (26894 hom., cov: 33)
• Consequence: MSH2 NM_000251.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.58

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.07).
• BP6: Variant 2-47418110-G-T is Benign according to our data. Variant chr2-47418110-G-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSH2	NM_000251.3	c.1076+1681G>T		intron_variant		ENST00000233146.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSH2	ENST00000233146.7	c.1076+1681G>T		intron_variant		1	NM_000251.3	P1

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86784 AN: 151926 Hom.: 26845 Cov.: 33

Gnomad AFR AF: 0.802

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.807

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.525

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

GnomAD4 genome AF: 0.571 AC: 86893 AN: 152044 Hom.: 26894 Cov.: 33 AF XY: 0.578 AC XY: 42971 AN XY: 74312

Gnomad4 AFR AF: 0.802

Gnomad4 AMR AF: 0.493

Gnomad4 ASJ AF: 0.402

Gnomad4 EAS AF: 0.807

Gnomad4 SAS AF: 0.543

Gnomad4 FIN AF: 0.609

Gnomad4 NFE AF: 0.437

Gnomad4 OTH AF: 0.526

Alfa AF: 0.476 Hom.: 7426

Bravo AF: 0.571

Asia WGS AF: 0.686 AC: 2387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	0.38
Dann	Benign	0.35

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: rs10191478; hg19: chr2-47645249;