9-2039776-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG

Position:

• chr9-2039776-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG

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_707dup​(p.Gln237dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0321 in 150,494 control chromosomes in the GnomAD database, including 130 homozygotes. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. Q222Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.032 (130 hom., cov: 26)
  • Exomes 𝑓: 0.017 (34 hom.)
  • Failed GnomAD Quality Control
• Consequence: SMARCA2 NM_003070.5 inframe_insertion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• 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-A-ACAG is Benign according to our data. Variant chr9-2039776-A-ACAG is described in ClinVar as [Benign]. Clinvar id is 436797.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMARCA2	NM_003070.5	c.705_707dup	p.Gln237dup	inframe_insertion	4/34	ENST00000349721.8
SMARCA2	NM_001289396.1	c.705_707dup	p.Gln237dup	inframe_insertion	4/34
SMARCA2	NM_001289397.2	c.705_707dup	p.Gln237dup	inframe_insertion	4/33
SMARCA2	NM_139045.4	c.705_707dup	p.Gln237dup	inframe_insertion	4/33

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCA2	ENST00000349721.8	c.705_707dup	p.Gln237dup	inframe_insertion	4/34	5	NM_003070.5	P2

Frequencies

GnomAD3 genomes AF: 0.0321 AC: 4824 AN: 150394 Hom.: 131 Cov.: 26

Gnomad AFR AF: 0.0679

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0168

Gnomad ASJ AF: 0.0208

Gnomad EAS AF: 0.0179

Gnomad SAS AF: 0.0199

Gnomad FIN AF: 0.0457

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0148

Gnomad OTH AF: 0.0315

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0168 AC: 24355 AN: 1445666 Hom.: 34 Cov.: 28 AF XY: 0.0170 AC XY: 12189 AN XY: 718498

Gnomad4 AFR exome AF: 0.0687

Gnomad4 AMR exome AF: 0.0151

Gnomad4 ASJ exome AF: 0.0172

Gnomad4 EAS exome AF: 0.0172

Gnomad4 SAS exome AF: 0.0202

Gnomad4 FIN exome AF: 0.0422

Gnomad4 NFE exome AF: 0.0136

Gnomad4 OTH exome AF: 0.0220

GnomAD4 genome AF: 0.0321 AC: 4837 AN: 150494 Hom.: 130 Cov.: 26 AF XY: 0.0327 AC XY: 2405 AN XY: 73466

Gnomad4 AFR AF: 0.0679

Gnomad4 AMR AF: 0.0172

Gnomad4 ASJ AF: 0.0208

Gnomad4 EAS AF: 0.0179

Gnomad4 SAS AF: 0.0199

Gnomad4 FIN AF: 0.0457

Gnomad4 NFE AF: 0.0148

Gnomad4 OTH AF: 0.0312

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 14, 2023	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 18, 2019	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 08, 2017	- -

Inborn genetic diseases Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 24, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Splicing

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;