9-2028942-A-G

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.-36-45A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 1,438,398 control chromosomes in the GnomAD database, including 10,038 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1015 hom., cov: 33)
  • Exomes 𝑓: 0.11 (9023 hom.)
• Consequence: SMARCA2 NM_003070.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.409

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=-0.56).
• BP6: Variant 9-2028942-A-G is Benign according to our data. Variant chr9-2028942-A-G is described in ClinVar as [Benign]. Clinvar id is 1251909.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMARCA2	NM_003070.5	c.-36-45A>G		intron_variant		ENST00000349721.8
SMARCA2	NM_001289396.1	c.-36-45A>G		intron_variant
SMARCA2	NM_001289397.2	c.-36-45A>G		intron_variant
SMARCA2	NM_139045.4	c.-36-45A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCA2	ENST00000349721.8	c.-36-45A>G		intron_variant		5	NM_003070.5	P2

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16280 AN: 152234 Hom.: 1009 Cov.: 33

Gnomad AFR AF: 0.0784

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.0813

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.0994

GnomAD4 exome AF: 0.113 AC: 144766 AN: 1286044 Hom.: 9023 Cov.: 19 AF XY: 0.113 AC XY: 71898 AN XY: 638992

Gnomad4 AFR exome AF: 0.0788

Gnomad4 AMR exome AF: 0.111

Gnomad4 ASJ exome AF: 0.0804

Gnomad4 EAS exome AF: 0.263

Gnomad4 SAS exome AF: 0.133

Gnomad4 FIN exome AF: 0.138

Gnomad4 NFE exome AF: 0.107

Gnomad4 OTH exome AF: 0.110

GnomAD4 genome AF: 0.107 AC: 16302 AN: 152354 Hom.: 1015 Cov.: 33 AF XY: 0.109 AC XY: 8129 AN XY: 74498

Gnomad4 AFR AF: 0.0785

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.0813

Gnomad4 EAS AF: 0.259

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0962 Hom.: 752

Bravo AF: 0.101

Asia WGS AF: 0.230 AC: 799 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

Aug 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
Cadd	Benign	18
Dann	Benign	0.81

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: rs10964466; hg19: chr9-2028942;