9-2120825-G-A

Variant names:

• chr9-2120825-G-A
• rs2001776
• NM_003070.5:c.3762+1290G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

SMARCA2 Gene-Disease associations (from GenCC):

• intellectual disability-sparse hair-brachydactyly syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003070.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCA2	NM_003070.5	MANE Select	c.3762+1290G>A		intron	N/A	NP_003061.3
	SMARCA2	NM_001289396.2		c.3762+1290G>A		intron	N/A	NP_001276325.1
	SMARCA2	NM_139045.4		c.3762+1290G>A		intron	N/A	NP_620614.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCA2	ENST00000349721.8	TSL:5 MANE Select	c.3762+1290G>A		intron	N/A	ENSP00000265773.5
	SMARCA2	ENST00000382203.5	TSL:1	c.3762+1290G>A		intron	N/A	ENSP00000371638.1
	SMARCA2	ENST00000450198.6	TSL:1	c.3588+1290G>A		intron	N/A	ENSP00000392081.2

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

African (AFR) AF: 0.387 AC: 16031 AN: 41448

American (AMR) AF: 0.182 AC: 2785 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 454 AN: 3468

East Asian (EAS) AF: 0.360 AC: 1858 AN: 5168

South Asian (SAS) AF: 0.162 AC: 781 AN: 4826

European-Finnish (FIN) AF: 0.107 AC: 1137 AN: 10588

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0758 AC: 5153 AN: 67984

Other (OTH) AF: 0.166 AC: 352 AN: 2116

Alfa AF: 0.107 Hom.: 2743

Bravo AF: 0.202

Asia WGS AF: 0.254 AC: 887 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.10
DANN	Benign	0.65
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2001776; hg19: chr9-2120825;