2-47414420-TAAAAAAAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAA

Variant names:

• chr2-47414420-TAAA-T
• rs11309117
• NM_000251.3:c.942+27_942+29delAAA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The ENST00000233146.7(MSH2):​c.942+3_942+5delAAA variant causes a splice region, intron change. The variant allele was found at a frequency of 0.156 in 949,752 control chromosomes in the GnomAD database, including 472 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.058 (57 hom., cov: 0)
  • Exomes 𝑓: 0.16 (472 hom.)
  • Failed GnomAD Quality Control
• Consequence: MSH2 ENST00000233146.7 splice_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• 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 -16 ACMG points.

• BP6: Variant 2-47414420-TAAA-T is Benign according to our data. Variant chr2-47414420-TAAA-T is described in ClinVar as [Likely_benign]. Clinvar id is 439908.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414420-TAAA-T is described in Lovd as [Benign]. Variant chr2-47414420-TAAA-T is described in Lovd as [Likely_benign].
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSH2	NM_000251.3	c.942+27_942+29delAAA		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+5delAAA		splice_region_variant, intron_variant	Intron 5 of 15	1	NM_000251.3	ENSP00000233146.2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 3632 AN: 62322 Hom.: 57 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.0796

Gnomad AMI AF: 0.0608

Gnomad AMR AF: 0.0405

Gnomad ASJ AF: 0.0102

Gnomad EAS AF: 0.00245

Gnomad SAS AF: 0.0108

Gnomad FIN AF: 0.0833

Gnomad MID AF: 0.0200

Gnomad NFE AF: 0.0549

Gnomad OTH AF: 0.0398

GnomAD3 exomes AF: 0.136 AC: 7135 AN: 52420 Hom.: 2 AF XY: 0.129 AC XY: 3623 AN XY: 28096

Gnomad AFR exome AF: 0.113

Gnomad AMR exome AF: 0.177

Gnomad ASJ exome AF: 0.139

Gnomad EAS exome AF: 0.186

Gnomad SAS exome AF: 0.129

Gnomad FIN exome AF: 0.0563

Gnomad NFE exome AF: 0.123

Gnomad OTH exome AF: 0.160

GnomAD4 exome AF: 0.156 AC: 148191 AN: 949752 Hom.: 472 AF XY: 0.155 AC XY: 73276 AN XY: 471362

Gnomad4 AFR exome AF: 0.138

Gnomad4 AMR exome AF: 0.143

Gnomad4 ASJ exome AF: 0.145

Gnomad4 EAS exome AF: 0.167

Gnomad4 SAS exome AF: 0.146

Gnomad4 FIN exome AF: 0.155

Gnomad4 NFE exome AF: 0.157

Gnomad4 OTH exome AF: 0.160

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0583 AC: 3632 AN: 62324 Hom.: 57 Cov.: 0 AF XY: 0.0578 AC XY: 1594 AN XY: 27596

Gnomad4 AFR AF: 0.0796

Gnomad4 AMR AF: 0.0405

Gnomad4 ASJ AF: 0.0102

Gnomad4 EAS AF: 0.00245

Gnomad4 SAS AF: 0.00998

Gnomad4 FIN AF: 0.0833

Gnomad4 NFE AF: 0.0549

Gnomad4 OTH AF: 0.0397

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 04, 2022

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:2

Aug 07, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 26, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Lynch syndrome 1 Benign:1

Jan 01, 2019

Institute of Human Genetics, University of Leipzig Medical Center

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary nonpolyposis colorectal neoplasms Benign:1

Dec 27, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary cancer-predisposing syndrome Benign:1

Nov 22, 2021

Sema4, Sema4

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: curation

- -

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;