9-2029018-G-A

Position:

chr9-2029018-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003070.5(SMARCA2):c.-5G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0976 in 1,547,988 control chromosomes in the GnomAD database, including 8,722 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1599 hom., cov: 33)

Exomes 𝑓: 0.094 ( 7123 hom. )

Consequence

SMARCA2
NM_003070.5 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.00500

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 9-2029018-G-A is Benign according to our data. Variant chr9-2029018-G-A is described in ClinVar as [Benign]. Clinvar id is 126341.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
SMARCA2	NM_003070.5 linkuse as main transcript	c.-5G>A	5_prime_UTR_variant	2/34	ENST00000349721.8
SMARCA2	NM_001289396.1 linkuse as main transcript	c.-5G>A	5_prime_UTR_variant	2/34
SMARCA2	NM_001289397.2 linkuse as main transcript	c.-5G>A	5_prime_UTR_variant	2/33
SMARCA2	NM_139045.4 linkuse as main transcript	c.-5G>A	5_prime_UTR_variant	2/33

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCA2	ENST00000349721.8 linkuse as main transcript	c.-5G>A		5_prime_UTR_variant	2/34	5	NM_003070.5	P2	P51531-1

Frequencies

GnomAD3 genomes

AF:

0.130

AC:

19743

AN:

152192

Hom.:

1590

Cov.:

show subpopulations

Gnomad AFR

AF:

0.216

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.195

Gnomad ASJ

AF:

0.0807

Gnomad EAS

AF:

0.114

Gnomad SAS

AF:

0.0750

Gnomad FIN

AF:

0.0578

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0842

Gnomad OTH

AF:

0.110

GnomAD3 exomes

AF:

0.115

AC:

17070

AN:

149066

Hom.:

1394

AF XY:

0.108

AC XY:

8586

AN XY:

79660

show subpopulations

Gnomad AFR exome

AF:

0.219

Gnomad AMR exome

AF:

0.249

Gnomad ASJ exome

AF:

0.0766

Gnomad EAS exome

AF:

0.126

Gnomad SAS exome

AF:

0.0704

Gnomad FIN exome

AF:

0.0511

Gnomad NFE exome

AF:

0.0833

Gnomad OTH exome

AF:

0.0969

GnomAD4 exome

AF:

0.0940

AC:

131232

AN:

1395678

Hom.:

7123

Cov.:

AF XY:

0.0922

AC XY:

63467

AN XY:

688540

show subpopulations

Gnomad4 AFR exome

AF:

0.219

Gnomad4 AMR exome

AF:

0.244

Gnomad4 ASJ exome

AF:

0.0783

Gnomad4 EAS exome

AF:

0.141

Gnomad4 SAS exome

AF:

0.0716

Gnomad4 FIN exome

AF:

0.0522

Gnomad4 NFE exome

AF:

0.0879

Gnomad4 OTH exome

AF:

0.0970

GnomAD4 genome

AF:

0.130

AC:

19787

AN:

152310

Hom.:

1599

Cov.:

AF XY:

0.129

AC XY:

9610

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.216

Gnomad4 AMR

AF:

0.195

Gnomad4 ASJ

AF:

0.0807

Gnomad4 EAS

AF:

0.114

Gnomad4 SAS

AF:

0.0749

Gnomad4 FIN

AF:

0.0578

Gnomad4 NFE

AF:

0.0842

Gnomad4 OTH

AF:

0.112

Alfa

AF:

0.0999

Hom.:

815

Bravo

AF:

0.148

Asia WGS

AF:

0.116

AC:

403

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 03, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Aug 15, 2013

- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 24, 2016

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

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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

-0.64

CADD

Benign

9.6

DANN

Benign

0.93

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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