2-47414420-TAAAAAAAAAAAAAAAAAAA-TAAA

Position:

• chr2-47414420-TAAAAAAAAAAAAAAAAAAA-TAAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP6_Very_Strong

The NM_000251.3(MSH2):​c.942+14_942+29del variant causes a splice donor 5th base, intron change. The variant allele was found at a frequency of 0.0000469 in 1,044,402 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000064 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000046 (0 hom.)
• Consequence: MSH2 NM_000251.3 splice_donor_5th_base, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 6.75

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 -8 ACMG points.

• BP6: Variant 2-47414420-TAAAAAAAAAAAAAAAA-T is Benign according to our data. Variant chr2-47414420-TAAAAAAAAAAAAAAAA-T is described in ClinVar as [Likely_benign]. Clinvar id is 983056.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSH2	NM_000251.3	c.942+14_942+29del		splice_donor_5th_base_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+14_942+29del		splice_donor_5th_base_variant, intron_variant		1	NM_000251.3	ENSP00000233146	P1

Frequencies

GnomAD3 genomes AF: 0.0000643 AC: 4 AN: 62234 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000124

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000458 AC: 45 AN: 982168 Hom.: 0 AF XY: 0.0000451 AC XY: 22 AN XY: 488170

Gnomad4 AFR exome AF: 0.0000926

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000174

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000511

Gnomad4 OTH exome AF: 0.0000519

GnomAD4 genome AF: 0.0000643 AC: 4 AN: 62234 Hom.: 0 Cov.: 0 AF XY: 0.0000363 AC XY: 1 AN XY: 27562

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000124

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Hereditary cancer-predisposing syndrome Benign:1

Likely benign, criteria provided, single submitter

curation

Sema4, Sema4

Nov 18, 2020

- -

Breast carcinoma Benign:1

Benign, criteria provided, single submitter

clinical testing

Institute of Human Genetics, University of Leipzig Medical Center

Jan 01, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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;