rs10964907

Variant names:

• chr9-2129798-T-G
• rs10964907
• NM_003070.5:c.3981+5861T>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.3981+5861T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 152,042 control chromosomes in the GnomAD database, including 11,698 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 0.29 (11698 hom., cov: 32)
• Consequence: SMARCA2 NM_003070.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.352
• 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: PanelApp Australia, Orphanet, G2P, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• blepharophimosis-impaired intellectual development syndrome

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.693 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCA2	NM_003070.5	MANE Select	c.3981+5861T>G		intron	N/A	NP_003061.3
	SMARCA2	NM_001289396.2		c.3981+5861T>G		intron	N/A	NP_001276325.1	P51531-1
	SMARCA2	NM_139045.4		c.3981+5861T>G		intron	N/A	NP_620614.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCA2	ENST00000349721.8	TSL:5 MANE Select	c.3981+5861T>G		intron	N/A	ENSP00000265773.5	P51531-1
	SMARCA2	ENST00000382203.5	TSL:1	c.3981+5861T>G		intron	N/A	ENSP00000371638.1	P51531-1
	SMARCA2	ENST00000450198.6	TSL:1	c.3807+5861T>G		intron	N/A	ENSP00000392081.2	F6VDE0

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44042 AN: 151924 Hom.: 11647 Cov.: 32

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.0901

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.0907

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.290 AC: 44154 AN: 152042 Hom.: 11698 Cov.: 32 AF XY: 0.288 AC XY: 21418 AN XY: 74346

African (AFR) AF: 0.699 AC: 28976 AN: 41434

American (AMR) AF: 0.187 AC: 2864 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 362 AN: 3468

East Asian (EAS) AF: 0.439 AC: 2260 AN: 5144

South Asian (SAS) AF: 0.222 AC: 1065 AN: 4808

European-Finnish (FIN) AF: 0.0907 AC: 961 AN: 10598

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 7027 AN: 67990

Other (OTH) AF: 0.241 AC: 510 AN: 2116

Alfa AF: 0.157 Hom.: 7739

Bravo AF: 0.317

Asia WGS AF: 0.332 AC: 1157 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.4
DANN	Benign	0.56
PhyloP100		0.35
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: rs10964907; hg19: chr9-2129798;