chr2-47790891-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000179.3(MSH6):c.261-36A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0503 in 1,605,144 control chromosomes in the GnomAD database, including 2,371 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).

Frequency

Genomes: 𝑓 0.036 ( 131 hom., cov: 33)

Exomes 𝑓: 0.052 ( 2240 hom. )

Consequence

MSH6
NM_000179.3 intron

Scores

Clinical Significance

Benign reviewed by expert panel B:6

Conservation

PhyloP100: 0.414

Publications

4 publications found

Variant links:

Genes affected

MSH6 (HGNC:7329): (mutS homolog 6) This gene encodes a member of the DNA mismatch repair MutS family. In E. coli, the MutS protein helps in the recognition of mismatched nucleotides prior to their repair. A highly conserved region of approximately 150 aa, called the Walker-A adenine nucleotide binding motif, exists in MutS homologs. The encoded protein heterodimerizes with MSH2 to form a mismatch recognition complex that functions as a bidirectional molecular switch that exchanges ADP and ATP as DNA mismatches are bound and dissociated. Mutations in this gene may be associated with hereditary nonpolyposis colon cancer, colorectal cancer, and endometrial cancer. Transcripts variants encoding different isoforms have been described. [provided by RefSeq, Jul 2013]

MSH6 links:

FBXO11 (HGNC:13590): (F-box protein 11) This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbxs class. It can function as an arginine methyltransferase that symmetrically dimethylates arginine residues, and it acts as an adaptor protein to mediate the neddylation of p53, which leads to the suppression of p53 function. This gene is known to be down-regulated in melanocytes from patients with vitiligo, a skin disorder that results in depigmentation. Polymorphisms in this gene are associated with chronic otitis media with effusion and recurrent otitis media (COME/ROM), a hearing loss disorder, and the knockout of the homologous mouse gene results in the deaf mouse mutant Jeff (Jf), a single gene model of otitis media. Alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jun 2010]

FBXO11 Gene-Disease associations (from GenCC):

intellectual developmental disorder with dysmorphic facies and behavioral abnormalities
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

FBXO11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 2-47790891-A-G is Benign according to our data. Variant chr2-47790891-A-G is described in ClinVar as [Benign]. Clinvar id is 89301.Status of the report is reviewed_by_expert_panel, 3 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSH6	NM_000179.3 link	c.261-36A>G		intron_variant	Intron 1 of 9	ENST00000234420.11	NP_000170.1	P52701-1Q3SWU9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSH6	ENST00000234420.11 link	c.261-36A>G		intron_variant	Intron 1 of 9	1	NM_000179.3	ENSP00000234420.5		P52701-1

Frequencies

GnomAD3 genomes

AF:

0.0357

AC:

5432

AN:

152184

Hom.:

131

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0107

Gnomad AMI

AF:

0.0570

Gnomad AMR

AF:

0.0380

Gnomad ASJ

AF:

0.0153

Gnomad EAS

AF:

0.0229

Gnomad SAS

AF:

0.0170

Gnomad FIN

AF:

0.0267

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0552

Gnomad OTH

AF:

0.0297

GnomAD2 exomes

AF:

0.0373

AC:

9344

AN:

250766

AF XY:

0.0373

show subpopulations

Gnomad AFR exome

AF:

0.00906

Gnomad AMR exome

AF:

0.0338

Gnomad ASJ exome

AF:

0.0150

Gnomad EAS exome

AF:

0.0190

Gnomad FIN exome

AF:

0.0315

Gnomad NFE exome

AF:

0.0542

Gnomad OTH exome

AF:

0.0335

GnomAD4 exome

AF:

0.0518

AC:

75283

AN:

1452842

Hom.:

2240

Cov.:

AF XY:

0.0508

AC XY:

36754

AN XY:

723460

show subpopulations

African (AFR)

AF:

0.00786

AC:

262

AN:

33322

American (AMR)

AF:

0.0342

AC:

1527

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.0140

AC:

366

AN:

26088

East Asian (EAS)

AF:

0.0200

AC:

795

AN:

39678

South Asian (SAS)

AF:

0.0199

AC:

1713

AN:

86032

European-Finnish (FIN)

AF:

0.0347

AC:

1854

AN:

53410

Middle Eastern (MID)

AF:

0.00922

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.0600

AC:

66185

AN:

1103744

Other (OTH)

AF:

0.0421

AC:

2528

AN:

60104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

3617

7234

10850

14467

18084

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0356

AC:

5429

AN:

152302

Hom.:

131

Cov.:

AF XY:

0.0334

AC XY:

2490

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.0107

AC:

443

AN:

41578

American (AMR)

AF:

0.0379

AC:

579

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.0153

AC:

AN:

3472

East Asian (EAS)

AF:

0.0227

AC:

118

AN:

5188

South Asian (SAS)

AF:

0.0168

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0267

AC:

284

AN:

10620

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0552

AC:

3753

AN:

68024

Other (OTH)

AF:

0.0294

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

264

527

791

1054

1318

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0465

Hom.:

292

Bravo

AF:

0.0352

Asia WGS

AF:

0.0210

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

not specified

Benign:2

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 19, 2018

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Lynch syndrome 5

Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Lynch syndrome

Benign:1

Sep 05, 2013

International Society for Gastrointestinal Hereditary Tumours (InSiGHT)

Significance:Benign

Review Status:reviewed by expert panel

Collection Method:research

MAF >1% -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Benign

0.77

PhyloP100

0.41

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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chr2-47790891-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over