2-47414420-TAAAAAAAAAAAAAAAAAAA-TAAAAAAA

Variant names:

• chr2-47414420-TAAAAAAAAAAAA-T
• rs11309117
• NM_000251.3:c.942+18_942+29delAAAAAAAAAAAA

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS1

The ENST00000233146.7(MSH2):​c.942+3_942+14delAAAAAAAAAAAA variant causes a splice region, intron change. The variant allele was found at a frequency of 0.000305 in 1,044,300 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00051 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00029 (0 hom.)
• Consequence: MSH2 ENST00000233146.7 splice_region, intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• 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 -12 ACMG points.

• BP6: Variant 2-47414420-TAAAAAAAAAAAA-T is Benign according to our data. Variant chr2-47414420-TAAAAAAAAAAAA-T is described in ClinVar as [Likely_benign]. Clinvar id is 1692301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000514 (32/62240) while in subpopulation SAS AF= 0.0154 (17/1106). AF 95% confidence interval is 0.00979. There are 0 homozygotes in gnomad4. There are 20 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSH2	NM_000251.3	c.942+18_942+29delAAAAAAAAAAAA		intron_variant	Intron 5 of 15	ENST00000233146.7	NP_000242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSH2	ENST00000233146.7	c.942+3_942+14delAAAAAAAAAAAA		splice_region_variant, intron_variant	Intron 5 of 15	1	NM_000251.3	ENSP00000233146.2

Frequencies

GnomAD3 genomes AF: 0.000514 AC: 32 AN: 62238 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000258

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000242

Gnomad ASJ AF: 0.00113

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0153

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000217

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000291 AC: 286 AN: 982060 Hom.: 0 AF XY: 0.000359 AC XY: 175 AN XY: 488110

Gnomad4 AFR exome AF: 0.000880

Gnomad4 AMR exome AF: 0.000589

Gnomad4 ASJ exome AF: 0.00244

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00228

Gnomad4 FIN exome AF: 0.0000466

Gnomad4 NFE exome AF: 0.0000932

Gnomad4 OTH exome AF: 0.000389

GnomAD4 genome AF: 0.000514 AC: 32 AN: 62240 Hom.: 0 Cov.: 0 AF XY: 0.000725 AC XY: 20 AN XY: 27572

Gnomad4 AFR AF: 0.000258

Gnomad4 AMR AF: 0.000242

Gnomad4 ASJ AF: 0.00113

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0154

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000217

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary nonpolyposis colorectal neoplasms Benign:1

Dec 02, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary cancer-predisposing syndrome Benign:1

Apr 22, 2021

Sema4, Sema4

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: curation

- -

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;