rs10512034

Positions:

• chr9-2000684-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000637383.1(SMARCA2):​c.-37+20298G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0871 in 151,982 control chromosomes in the GnomAD database, including 821 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.087 (821 hom., cov: 31)
• Consequence: SMARCA2 ENST00000637383.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.104

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMARCA2	ENST00000637383.1	c.-37+20298G>A		intron_variant		5		ENSP00000489645

Frequencies

GnomAD3 genomes AF: 0.0870 AC: 13215 AN: 151864 Hom.: 815 Cov.: 31

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0774

Gnomad ASJ AF: 0.0504

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.0800

Gnomad FIN AF: 0.0490

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0442

Gnomad OTH AF: 0.0835

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0871 AC: 13234 AN: 151982 Hom.: 821 Cov.: 31 AF XY: 0.0878 AC XY: 6518 AN XY: 74278

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.0773

Gnomad4 ASJ AF: 0.0504

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.0797

Gnomad4 FIN AF: 0.0490

Gnomad4 NFE AF: 0.0442

Gnomad4 OTH AF: 0.0878

Alfa AF: 0.0560 Hom.: 139

Bravo AF: 0.0919

Asia WGS AF: 0.188 AC: 652 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.0
DANN	Benign	0.78

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10512034; hg19: chr9-2000684;