rs10964471

Variant names:

• chr9-2029199-G-A
• rs10964471
• NM_003070.5:c.177G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-2029199-G-A
• chr9-2029199-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_003070.5(SMARCA2):​c.177G>A​(p.Thr59Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0936 in 1,613,014 control chromosomes in the GnomAD database, including 8,089 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.082 (694 hom., cov: 33)
  • Exomes 𝑓: 0.095 (7395 hom.)
• Consequence: SMARCA2 NM_003070.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -5.89
• Publications: 14 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 9-2029199-G-A is Benign according to our data. Variant chr9-2029199-G-A is described in ClinVar as Benign. ClinVar VariationId is 126344.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.89 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.223 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.177G>A	p.Thr59Thr	synonymous	Exon 2 of 34	NP_003061.3
	SMARCA2	NM_001289396.2		c.177G>A	p.Thr59Thr	synonymous	Exon 2 of 34	NP_001276325.1	P51531-1
	SMARCA2	NM_139045.4		c.177G>A	p.Thr59Thr	synonymous	Exon 2 of 33	NP_620614.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCA2	ENST00000349721.8	TSL:5 MANE Select	c.177G>A	p.Thr59Thr	synonymous	Exon 2 of 34	ENSP00000265773.5	P51531-1
	SMARCA2	ENST00000382203.5	TSL:1	c.177G>A	p.Thr59Thr	synonymous	Exon 2 of 34	ENSP00000371638.1	P51531-1
	SMARCA2	ENST00000450198.6	TSL:1	c.177G>A	p.Thr59Thr	synonymous	Exon 2 of 33	ENSP00000392081.2	F6VDE0

Frequencies

GnomAD3 genomes AF: 0.0818 AC: 12446 AN: 152202 Hom.: 693 Cov.: 33

Gnomad AFR AF: 0.0294

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0720

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0885

Gnomad OTH AF: 0.0837

GnomAD2 exomes AF: 0.105 AC: 26082 AN: 249134 AF XY: 0.106

Gnomad AFR exome AF: 0.0291

Gnomad AMR exome AF: 0.106

Gnomad ASJ exome AF: 0.0689

Gnomad EAS exome AF: 0.224

Gnomad FIN exome AF: 0.121

Gnomad NFE exome AF: 0.0904

Gnomad OTH exome AF: 0.0993

GnomAD4 exome AF: 0.0948 AC: 138485 AN: 1460694 Hom.: 7395 Cov.: 33 AF XY: 0.0951 AC XY: 69070 AN XY: 726506

African (AFR) AF: 0.0254 AC: 850 AN: 33466

American (AMR) AF: 0.105 AC: 4674 AN: 44604

Ashkenazi Jewish (ASJ) AF: 0.0676 AC: 1764 AN: 26098

East Asian (EAS) AF: 0.232 AC: 9214 AN: 39674

South Asian (SAS) AF: 0.122 AC: 10465 AN: 85968

European-Finnish (FIN) AF: 0.125 AC: 6692 AN: 53364

Middle Eastern (MID) AF: 0.0304 AC: 175 AN: 5766

European-Non Finnish (NFE) AF: 0.0891 AC: 99032 AN: 1111404

Other (OTH) AF: 0.0931 AC: 5619 AN: 60350

GnomAD4 genome AF: 0.0817 AC: 12451 AN: 152320 Hom.: 694 Cov.: 33 AF XY: 0.0855 AC XY: 6366 AN XY: 74490

African (AFR) AF: 0.0293 AC: 1220 AN: 41584

American (AMR) AF: 0.105 AC: 1604 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0720 AC: 250 AN: 3470

East Asian (EAS) AF: 0.234 AC: 1211 AN: 5176

South Asian (SAS) AF: 0.141 AC: 679 AN: 4824

European-Finnish (FIN) AF: 0.118 AC: 1255 AN: 10606

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0885 AC: 6023 AN: 68032

Other (OTH) AF: 0.0875 AC: 185 AN: 2114

Alfa AF: 0.0767 Hom.: 800

Bravo AF: 0.0750

Asia WGS AF: 0.203 AC: 705 AN: 3478

EpiCase AF: 0.0800

EpiControl AF: 0.0773

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Inborn genetic diseases (1)
-	-	1	Nicolaides-Baraitser syndrome (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.13
DANN	Benign	0.74
PhyloP100		-5.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10964471; hg19: chr9-2029199; COSMIC: COSV61808078; COSMIC: COSV61808078;