rs2001776

Positions:

• chr9-2120825-G-A
• chr9-2120825-G-C

Variant summary

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

The NM_003070.5(SMARCA2):​c.3762+1290G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,088 control chromosomes in the GnomAD database, including 4,123 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 0.19 (4123 hom., cov: 33)
• Consequence: SMARCA2 NM_003070.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMARCA2	NM_003070.5	c.3762+1290G>A		intron_variant		ENST00000349721.8	NP_003061.3
SMARCA2	NM_001289396.1	c.3762+1290G>A		intron_variant			NP_001276325.1
SMARCA2	NM_001289397.2	c.3588+1290G>A		intron_variant			NP_001276326.1
SMARCA2	NM_139045.4	c.3762+1290G>A		intron_variant			NP_620614.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMARCA2	ENST00000349721.8	c.3762+1290G>A		intron_variant		5	NM_003070.5	ENSP00000265773	P2

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28560 AN: 151970 Hom.: 4117 Cov.: 33

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0758

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.188 AC: 28606 AN: 152088 Hom.: 4123 Cov.: 33 AF XY: 0.191 AC XY: 14178 AN XY: 74358

Gnomad4 AFR AF: 0.387

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.360

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.0758

Gnomad4 OTH AF: 0.166

Alfa AF: 0.0914 Hom.: 1355

Bravo AF: 0.202

Asia WGS AF: 0.254 AC: 887 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.10
DANN	Benign	0.65

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: rs2001776; hg19: chr9-2120825;