9-2039776-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAG

Variant names:

• chr9-2039776-ACAGCAGCAGCAGCAG-A
• rs113070757
• NM_003070.5:c.693_707delGCAGCAGCAGCAGCA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_003070.5(SMARCA2):​c.693_707delGCAGCAGCAGCAGCA​(p.Gln232_Gln236del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00351 in 150,530 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0035 (0 hom., cov: 26)
  • Exomes 𝑓: 0.0047 (12 hom.)
  • Failed GnomAD Quality Control
• Consequence: SMARCA2 NM_003070.5 disruptive_inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 1.94

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-ACAGCAGCAGCAGCAG-A is Benign according to our data. Variant chr9-2039776-ACAGCAGCAGCAGCAG-A is described in ClinVar as [Likely_benign]. Clinvar id is 212230.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-2039776-ACAGCAGCAGCAGCAG-A is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00351 (528/150530) while in subpopulation NFE AF= 0.00491 (332/67584). AF 95% confidence interval is 0.00448. There are 0 homozygotes in gnomad4. There are 231 alleles in male gnomad4 subpopulation. Median coverage is 26. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 528 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCA2	NM_003070.5	c.693_707delGCAGCAGCAGCAGCA	p.Gln232_Gln236del	disruptive_inframe_deletion	Exon 4 of 34	ENST00000349721.8	NP_003061.3
SMARCA2	NM_001289396.2	c.693_707delGCAGCAGCAGCAGCA	p.Gln232_Gln236del	disruptive_inframe_deletion	Exon 4 of 34		NP_001276325.1
SMARCA2	NM_139045.4	c.693_707delGCAGCAGCAGCAGCA	p.Gln232_Gln236del	disruptive_inframe_deletion	Exon 4 of 33		NP_620614.2
SMARCA2	NM_001289397.2	c.693_707delGCAGCAGCAGCAGCA	p.Gln232_Gln236del	disruptive_inframe_deletion	Exon 4 of 33		NP_001276326.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCA2	ENST00000349721.8	c.693_707delGCAGCAGCAGCAGCA	p.Gln232_Gln236del	disruptive_inframe_deletion	Exon 4 of 34	5	NM_003070.5	ENSP00000265773.5

Frequencies

GnomAD3 genomes AF: 0.00351 AC: 528 AN: 150430 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.000981

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00351

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.000981

Gnomad SAS AF: 0.000212

Gnomad FIN AF: 0.00482

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00491

Gnomad OTH AF: 0.00532

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00468 AC: 6760 AN: 1445818 Hom.: 12 AF XY: 0.00452 AC XY: 3246 AN XY: 718570

Gnomad4 AFR exome AF: 0.00119

Gnomad4 AMR exome AF: 0.00302

Gnomad4 ASJ exome AF: 0.0116

Gnomad4 EAS exome AF: 0.000130

Gnomad4 SAS exome AF: 0.000212

Gnomad4 FIN exome AF: 0.00559

Gnomad4 NFE exome AF: 0.00517

Gnomad4 OTH exome AF: 0.00425

GnomAD4 genome AF: 0.00351 AC: 528 AN: 150530 Hom.: 0 Cov.: 26 AF XY: 0.00314 AC XY: 231 AN XY: 73486

Gnomad4 AFR AF: 0.000978

Gnomad4 AMR AF: 0.00350

Gnomad4 ASJ AF: 0.0104

Gnomad4 EAS AF: 0.000984

Gnomad4 SAS AF: 0.000212

Gnomad4 FIN AF: 0.00482

Gnomad4 NFE AF: 0.00491

Gnomad4 OTH AF: 0.00526

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:6

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Nov 05, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 22, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Aug 29, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SMARCA2: BS1, BS2 -

not specified Benign:1

Jul 24, 2015

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases Benign:1

Oct 07, 2018

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely 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;