rs10964501

Variant names:

• chr9-2034553-T-A
• rs10964501
• NM_003070.5:c.355+1472T>A

Your query was ambiguous. Multiple possible variants found:

• chr9-2034553-T-A
• chr9-2034553-T-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.355+1472T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 152,068 control chromosomes in the GnomAD database, including 20,998 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 0.46 (20998 hom., cov: 32)
• Consequence: SMARCA2 NM_003070.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340
• Publications: 2 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.846 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCA2	NM_003070.5	c.355+1472T>A		intron_variant	Intron 3 of 33	ENST00000349721.8	NP_003061.3
SMARCA2	NM_001289396.2	c.355+1472T>A		intron_variant	Intron 3 of 33		NP_001276325.1
SMARCA2	NM_139045.4	c.355+1472T>A		intron_variant	Intron 3 of 32		NP_620614.2
SMARCA2	NM_001289397.2	c.355+1472T>A		intron_variant	Intron 3 of 32		NP_001276326.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCA2	ENST00000349721.8	c.355+1472T>A		intron_variant	Intron 3 of 33	5	NM_003070.5	ENSP00000265773.5

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70135 AN: 151950 Hom.: 20924 Cov.: 32

Gnomad AFR AF: 0.853

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.462 AC: 70273 AN: 152068 Hom.: 20998 Cov.: 32 AF XY: 0.462 AC XY: 34321 AN XY: 74348

African (AFR) AF: 0.853 AC: 35425 AN: 41514

American (AMR) AF: 0.453 AC: 6911 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 908 AN: 3468

East Asian (EAS) AF: 0.379 AC: 1963 AN: 5176

South Asian (SAS) AF: 0.297 AC: 1432 AN: 4824

European-Finnish (FIN) AF: 0.348 AC: 3666 AN: 10548

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.279 AC: 18960 AN: 67950

Other (OTH) AF: 0.407 AC: 859 AN: 2112

Alfa AF: 0.403 Hom.: 1981

Bravo AF: 0.485

Asia WGS AF: 0.434 AC: 1508 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.44
DANN	Benign	0.52
PhyloP100		-0.34
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: rs10964501; hg19: chr9-2034553;