9-2177492-A-G

Variant names:

• chr9-2177492-A-G
• rs10491697
• NM_003070.5:c.4254-4079A>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.4254-4079A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 151,958 control chromosomes in the GnomAD database, including 7,614 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 (7614 hom., cov: 32)
• Consequence: SMARCA2 NM_003070.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.888
• Publications: 5 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

LOC107987043 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCA2	NM_003070.5	c.4254-4079A>G		intron_variant	Intron 29 of 33	ENST00000349721.8	NP_003061.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCA2	ENST00000349721.8	c.4254-4079A>G		intron_variant	Intron 29 of 33	5	NM_003070.5	ENSP00000265773.5

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43894 AN: 151840 Hom.: 7598 Cov.: 32

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.289 AC: 43959 AN: 151958 Hom.: 7614 Cov.: 32 AF XY: 0.291 AC XY: 21608 AN XY: 74274

African (AFR) AF: 0.475 AC: 19686 AN: 41438

American (AMR) AF: 0.329 AC: 5030 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 734 AN: 3470

East Asian (EAS) AF: 0.375 AC: 1938 AN: 5170

South Asian (SAS) AF: 0.317 AC: 1525 AN: 4818

European-Finnish (FIN) AF: 0.199 AC: 2098 AN: 10542

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.179 AC: 12155 AN: 67944

Other (OTH) AF: 0.291 AC: 611 AN: 2102

Alfa AF: 0.215 Hom.: 7481

Bravo AF: 0.311

Asia WGS AF: 0.351 AC: 1219 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.4
DANN	Benign	0.74
PhyloP100		0.89
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: rs10491697; hg19: chr9-2177492; COSMIC: COSV56648605; COSMIC: COSV56648605;