chr2-47482014-G-A

Position:

• chr2-47482014-G-A

Variant summary

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

The NM_001406653.1(MSH2):​c.*1116G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 151,762 control chromosomes in the GnomAD database, including 22,211 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency: Genomes: 𝑓 0.51 (22211 hom., cov: 31)
• Consequence: MSH2 NM_001406653.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0140

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 2-47482014-G-A is Benign according to our data. Variant chr2-47482014-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSH2	NM_000251.3	c.2635-765G>A		intron_variant		ENST00000233146.7	NP_000242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSH2	ENST00000233146.7	c.2635-765G>A		intron_variant		1	NM_000251.3	ENSP00000233146.2

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77397 AN: 151644 Hom.: 22168 Cov.: 31

Gnomad AFR AF: 0.772

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.674

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.395

Gnomad NFE AF: 0.380

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.511 AC: 77500 AN: 151762 Hom.: 22211 Cov.: 31 AF XY: 0.512 AC XY: 37965 AN XY: 74130

Gnomad4 AFR AF: 0.773

Gnomad4 AMR AF: 0.404

Gnomad4 ASJ AF: 0.332

Gnomad4 EAS AF: 0.673

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.501

Gnomad4 NFE AF: 0.380

Gnomad4 OTH AF: 0.466

Alfa AF: 0.413 Hom.: 6664

Bravo AF: 0.514

Asia WGS AF: 0.562 AC: 1955 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.1
DANN	Benign	0.18

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: rs10188090; hg19: chr2-47709153;