9-2039776-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAGCAGCAGCAGCAG

Variant summary

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

The NM_003070.5(SMARCA2):c.705_707del(p.Gln238del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 1,427,642 control chromosomes in the GnomAD database, including 5,709 homozygotes. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. Q223Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.17 (2394 hom., cov: 26)
  • Exomes 𝑓: 0.14 (3315 hom.)
• Consequence: SMARCA2 NM_003070.5 inframe_deletion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.00

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 9-2039776-ACAG-A is Benign according to our data. Variant chr9-2039776-ACAG-A is described in ClinVar as [Benign]. Clinvar id is 126353.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-2039776-ACAG-A is described in Lovd as [Benign]. Variant chr9-2039776-ACAG-A is described in Lovd as [Likely_benign]. Variant chr9-2039776-ACAG-A is described in Lovd as [Benign]. Variant chr9-2039776-ACAG-A is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMARCA2	NM_003070.5	c.705_707del	p.Gln238del	inframe_deletion	4/34	ENST00000349721.8
SMARCA2	NM_001289396.1	c.705_707del	p.Gln238del	inframe_deletion	4/34
SMARCA2	NM_001289397.2	c.705_707del	p.Gln238del	inframe_deletion	4/33
SMARCA2	NM_139045.4	c.705_707del	p.Gln238del	inframe_deletion	4/33

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCA2	ENST00000349721.8	c.705_707del	p.Gln238del	inframe_deletion	4/34	5	NM_003070.5	P2

Frequencies

GnomAD3 genomes AF: 0.165 AC: 24790 AN: 150198 Hom.: 2377 Cov.: 26

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.0375

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.0833

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.0865

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.143

GnomAD4 exome AF: 0.143 AC: 183010 AN: 1277344 Hom.: 3315 AF XY: 0.144 AC XY: 90470 AN XY: 627376

Gnomad4 AFR exome AF: 0.233

Gnomad4 AMR exome AF: 0.207

Gnomad4 ASJ exome AF: 0.0978

Gnomad4 EAS exome AF: 0.354

Gnomad4 SAS exome AF: 0.183

Gnomad4 FIN exome AF: 0.192

Gnomad4 NFE exome AF: 0.127

Gnomad4 OTH exome AF: 0.156

GnomAD4 genome AF: 0.165 AC: 24843 AN: 150298 Hom.: 2394 Cov.: 26 AF XY: 0.168 AC XY: 12320 AN XY: 73378

Gnomad4 AFR AF: 0.238

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.0833

Gnomad4 EAS AF: 0.365

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.146

Bravo AF: 0.173

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 12, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 20, 2023	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Oct 24, 2013

- -

Inborn genetic diseases Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 16, 2022

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;C5443984:Blepharophimosis-impaired intellectual development syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Mar 30, 2022

- -

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: rs113070757; hg19: chr9-2039776;