rs1112534

chr9-2032845-G-Achr9-2032845-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003070.5(SMARCA2):c.226-107G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 974,010 control chromosomes in the GnomAD database, including 22,322 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4252 hom., cov: 32)
  • Exomes 𝑓: 0.20 (18070 hom.)
• Consequence: SMARCA2 NM_003070.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.372

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 9-2032845-G-A is Benign according to our data. Variant chr9-2032845-G-A is described in ClinVar as [Benign]. Clinvar id is 1235432.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMARCA2	NM_003070.5	c.226-107G>A		intron_variant		ENST00000349721.8
SMARCA2	NM_001289396.1	c.226-107G>A		intron_variant
SMARCA2	NM_001289397.2	c.226-107G>A		intron_variant
SMARCA2	NM_139045.4	c.226-107G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCA2	ENST00000349721.8	c.226-107G>A		intron_variant		5	NM_003070.5	P2

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34791 AN: 151992 Hom.: 4233 Cov.: 32

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.218

GnomAD4 exome AF: 0.204 AC: 167310 AN: 821900 Hom.: 18070 AF XY: 0.200 AC XY: 84187 AN XY: 420880

Gnomad4 AFR exome AF: 0.282

Gnomad4 AMR exome AF: 0.331

Gnomad4 ASJ exome AF: 0.150

Gnomad4 EAS exome AF: 0.335

Gnomad4 SAS exome AF: 0.170

Gnomad4 FIN exome AF: 0.214

Gnomad4 NFE exome AF: 0.192

Gnomad4 OTH exome AF: 0.201

GnomAD4 genome AF: 0.229 AC: 34846 AN: 152110 Hom.: 4252 Cov.: 32 AF XY: 0.232 AC XY: 17270 AN XY: 74378

Gnomad4 AFR AF: 0.279

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.308

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.224

Alfa AF: 0.181 Hom.: 1504

Bravo AF: 0.238

Asia WGS AF: 0.287 AC: 999 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	3.1
Dann	Benign	0.36

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: rs1112534; hg19: chr9-2032845; COSMIC: COSV104414050; COSMIC: COSV104414050;