Variant 2-47414420-TAAAAAAAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000251.3(MSH2):c.942+27_942+29del variant causes a splice donor 5th base, 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
NM_000251.3 splice_donor_5th_base, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 6.75

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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/exons	MANE	Protein	UniProt
MSH2	NM_000251.3 linkuse as main transcript	c.942+27_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 linkuse as main transcript	c.942+27_942+29del		splice_donor_5th_base_variant, intron_variant		1	NM_000251.3	ENSP00000233146	P1	P43246-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

3632

AN:

62322

Hom.:

Cov.:

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.:

AF XY:

0.129

AC XY:

3623

AN XY:

28096

show subpopulations

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

show subpopulations

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.:

Cov.:

AF XY:

0.0578

AC XY:

1594

AN XY:

27596

show subpopulations

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

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	Aug 15, 2023	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 04, 2022	- -
Benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 07, 2019	- -

Lynch syndrome 1

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Institute of Human Genetics, University of Leipzig Medical Center

Jan 01, 2019

- -

Hereditary nonpolyposis colorectal neoplasms

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 08, 2024

- -

Hereditary cancer-predisposing syndrome

Benign:1

Benign, criteria provided, single submitter

curation

Sema4, Sema4

Nov 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over