9-2095958-T-G

Variant names:

• chr9-2095958-T-G
• rs3793490
• NM_003070.5:c.2884-699T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003070.5(SMARCA2):​c.2884-699T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,198 control chromosomes in the GnomAD database, including 7,233 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 0.25 (7233 hom., cov: 32)
• Consequence: SMARCA2 NM_003070.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.59
• Publications: 10 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=-0.54).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCA2	NM_003070.5	c.2884-699T>G		intron_variant	Intron 19 of 33	ENST00000349721.8	NP_003061.3
SMARCA2	NM_001289396.2	c.2884-699T>G		intron_variant	Intron 19 of 33		NP_001276325.1
SMARCA2	NM_139045.4	c.2884-699T>G		intron_variant	Intron 19 of 32		NP_620614.2
SMARCA2	NM_001289397.2	c.2710-699T>G		intron_variant	Intron 19 of 32		NP_001276326.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCA2	ENST00000349721.8	c.2884-699T>G		intron_variant	Intron 19 of 33	5	NM_003070.5	ENSP00000265773.5

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37925 AN: 152080 Hom.: 7193 Cov.: 32

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.0924

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.250 AC: 38037 AN: 152198 Hom.: 7233 Cov.: 32 AF XY: 0.248 AC XY: 18472 AN XY: 74414

African (AFR) AF: 0.531 AC: 22055 AN: 41512

American (AMR) AF: 0.221 AC: 3384 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 560 AN: 3470

East Asian (EAS) AF: 0.269 AC: 1392 AN: 5184

South Asian (SAS) AF: 0.141 AC: 682 AN: 4826

European-Finnish (FIN) AF: 0.140 AC: 1480 AN: 10608

Middle Eastern (MID) AF: 0.103 AC: 30 AN: 292

European-Non Finnish (NFE) AF: 0.116 AC: 7920 AN: 67994

Other (OTH) AF: 0.221 AC: 468 AN: 2114

Alfa AF: 0.133 Hom.: 1139

Bravo AF: 0.270

Asia WGS AF: 0.259 AC: 901 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	17
DANN	Benign	0.73
PhyloP100		1.6
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: rs3793490; hg19: chr9-2095958;