rs10964471

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003070.5(SMARCA2):c.177G>A(p.Thr59Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0936 in 1,613,014 control chromosomes in the GnomAD database, including 8,089 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.082 ( 694 hom., cov: 33)

Exomes 𝑓: 0.095 ( 7395 hom. )

Consequence

SMARCA2
NM_003070.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -5.89

Variant links:

Genes affected

SMARCA2 (HGNC:11098): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 2) The protein encoded by this gene is a member of the SWI/SNF family of proteins and is highly similar to the brahma protein of Drosophila. Members of this family have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI, which is required for transcriptional activation of genes normally repressed by chromatin. Alternatively spliced transcript variants encoding different isoforms have been found for this gene, which contains a trinucleotide repeat (CAG) length polymorphism. [provided by RefSeq, Jan 2014]

SMARCA2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 9-2029199-G-A is Benign according to our data. Variant chr9-2029199-G-A is described in ClinVar as [Benign]. Clinvar id is 126344.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-5.89 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCA2	NM_003070.5 link	c.177G>A	p.Thr59Thr	synonymous_variant	Exon 2 of 34	ENST00000349721.8	NP_003061.3	P51531-1Q8N9Q1Q56A76
SMARCA2	NM_001289396.2 link	c.177G>A	p.Thr59Thr	synonymous_variant	Exon 2 of 34		NP_001276325.1	P51531-1Q8N9Q1B4DSC8
SMARCA2	NM_139045.4 link	c.177G>A	p.Thr59Thr	synonymous_variant	Exon 2 of 33		NP_620614.2	P51531-2Q8N9Q1Q56A76
SMARCA2	NM_001289397.2 link	c.177G>A	p.Thr59Thr	synonymous_variant	Exon 2 of 33		NP_001276326.1	P51531F6VDE0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCA2	ENST00000349721.8 link	c.177G>A	p.Thr59Thr	synonymous_variant	Exon 2 of 34	5	NM_003070.5	ENSP00000265773.5		P51531-1

Frequencies

GnomAD3 genomes

AF:

0.0818

AC:

12446

AN:

152202

Hom.:

693

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0294

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.105

Gnomad ASJ

AF:

0.0720

Gnomad EAS

AF:

0.235

Gnomad SAS

AF:

0.141

Gnomad FIN

AF:

0.118

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0885

Gnomad OTH

AF:

0.0837

GnomAD3 exomes

AF:

0.105

AC:

26082

AN:

249134

Hom.:

1619

AF XY:

0.106

AC XY:

14278

AN XY:

134752

show subpopulations

Gnomad AFR exome

AF:

0.0291

Gnomad AMR exome

AF:

0.106

Gnomad ASJ exome

AF:

0.0689

Gnomad EAS exome

AF:

0.224

Gnomad SAS exome

AF:

0.125

Gnomad FIN exome

AF:

0.121

Gnomad NFE exome

AF:

0.0904

Gnomad OTH exome

AF:

0.0993

GnomAD4 exome

AF:

0.0948

AC:

138485

AN:

1460694

Hom.:

7395

Cov.:

AF XY:

0.0951

AC XY:

69070

AN XY:

726506

show subpopulations

Gnomad4 AFR exome

AF:

0.0254

Gnomad4 AMR exome

AF:

0.105

Gnomad4 ASJ exome

AF:

0.0676

Gnomad4 EAS exome

AF:

0.232

Gnomad4 SAS exome

AF:

0.122

Gnomad4 FIN exome

AF:

0.125

Gnomad4 NFE exome

AF:

0.0891

Gnomad4 OTH exome

AF:

0.0931

GnomAD4 genome

AF:

0.0817

AC:

12451

AN:

152320

Hom.:

694

Cov.:

AF XY:

0.0855

AC XY:

6366

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0293

Gnomad4 AMR

AF:

0.105

Gnomad4 ASJ

AF:

0.0720

Gnomad4 EAS

AF:

0.234

Gnomad4 SAS

AF:

0.141

Gnomad4 FIN

AF:

0.118

Gnomad4 NFE

AF:

0.0885

Gnomad4 OTH

AF:

0.0875

Alfa

AF:

0.0771

Hom.:

654

Bravo

AF:

0.0750

Asia WGS

AF:

0.203

AC:

705

AN:

3478

EpiCase

AF:

0.0800

EpiControl

AF:

0.0773

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 08, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases

Benign:1

Mar 19, 2016

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Nicolaides-Baraitser syndrome

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.13

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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