rs113070757

chr9-2039776-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-Achr9-2039776-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGchr9-2039776-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGchr9-2039776-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGchr9-2039776-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGchr9-2039776-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAGchr9-2039776-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAGCAGchr9-2039776-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAGCAGCAGchr9-2039776-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAGCAGCAGCAGchr9-2039776-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAGCAGCAGCAGCAGchr9-2039776-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGchr9-2039776-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGchr9-2039776-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGchr9-2039776-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGchr9-2039776-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGchr9-2039776-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGchr9-2039776-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGchr9-2039776-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGchr9-2039776-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGchr9-2039776-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2 BP6_Moderate BS1 BS2

The NM_003070.5(SMARCA2):c.678_707del(p.Gln229_Gln238del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000266 in 150,532 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. Q223Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., cov: 26)
  • Exomes 𝑓: 0.000089 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SMARCA2 NM_003070.5 inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -8 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 9-2039776-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-A is Benign according to our data. Variant chr9-2039776-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-A is described in ClinVar as [Likely_benign]. Clinvar id is 1338913.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0000266 (4/150532) while in subpopulation AFR AF= 0.0000733 (3/40908). AF 95% confidence interval is 0.0000194. There are 0 homozygotes in gnomad4. There are 2 alleles in male gnomad4 subpopulation. Median coverage is 26. This position pass quality control queck.
• BS2: High AC in GnomAd at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMARCA2	NM_003070.5	c.678_707del	p.Gln229_Gln238del	inframe_deletion	4/34	ENST00000349721.8
SMARCA2	NM_001289396.1	c.678_707del	p.Gln229_Gln238del	inframe_deletion	4/34
SMARCA2	NM_001289397.2	c.678_707del	p.Gln229_Gln238del	inframe_deletion	4/33
SMARCA2	NM_139045.4	c.678_707del	p.Gln229_Gln238del	inframe_deletion	4/33

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCA2	ENST00000349721.8	c.678_707del	p.Gln229_Gln238del	inframe_deletion	4/34	5	NM_003070.5	P2

Frequencies

GnomAD3 genomes AF: 0.0000332 AC: 5 AN: 150432 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.0000735

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000212

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000885 AC: 128 AN: 1445816 Hom.: 0 AF XY: 0.0000738 AC XY: 53 AN XY: 718568

Gnomad4 AFR exome AF: 0.0000305

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000112

Gnomad4 OTH exome AF: 0.0000502

GnomAD4 genome AF: 0.0000266 AC: 4 AN: 150532 Hom.: 0 Cov.: 26 AF XY: 0.0000272 AC XY: 2 AN XY: 73486

Gnomad4 AFR AF: 0.0000733

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000148

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 24, 2021

- -

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;