2-47414420-TAAAAAAAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAAAAA

Position:

• chr2-47414420-TAAAAAAAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAAAAA

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_000251.3(MSH2):​c.942+29dup variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0023 (2 hom., cov: 0)
  • Exomes 𝑓: 0.0014 (0 hom.)
• Consequence: MSH2 NM_000251.3 splice_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.32

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.

• BP6: Variant 2-47414420-T-TA is Benign according to our data. Variant chr2-47414420-T-TA is described in ClinVar as [Likely_benign]. Clinvar id is 1685775.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSH2	NM_000251.3	c.942+29dup		splice_region_variant, intron_variant		ENST00000233146.7	NP_000242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSH2	ENST00000233146.7	c.942+29dup		splice_region_variant, intron_variant		1	NM_000251.3	ENSP00000233146	P1

Frequencies

GnomAD3 genomes AF: 0.00230 AC: 143 AN: 62206 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.00305

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00266

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000612

Gnomad SAS AF: 0.000904

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00199

Gnomad OTH AF: 0.00902

GnomAD4 exome AF: 0.00139 AC: 1362 AN: 980838 Hom.: 0 Cov.: 0 AF XY: 0.00139 AC XY: 677 AN XY: 487472

Gnomad4 AFR exome AF: 0.00209

Gnomad4 AMR exome AF: 0.00129

Gnomad4 ASJ exome AF: 0.00149

Gnomad4 EAS exome AF: 0.00106

Gnomad4 SAS exome AF: 0.00180

Gnomad4 FIN exome AF: 0.00126

Gnomad4 NFE exome AF: 0.00134

Gnomad4 OTH exome AF: 0.00164

GnomAD4 genome AF: 0.00230 AC: 143 AN: 62208 Hom.: 2 Cov.: 0 AF XY: 0.00200 AC XY: 55 AN XY: 27552

Gnomad4 AFR AF: 0.00305

Gnomad4 AMR AF: 0.00266

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000612

Gnomad4 SAS AF: 0.000907

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00199

Gnomad4 OTH AF: 0.00900

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	Feb 06, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 04, 2022	- -

Computational scores

Source: dbNSFP v4.3

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: rs11309117; hg19: chr2-47641559;