rs13288443

Variant names:

• chr9-2073292-A-G
• rs13288443
• NM_003070.5:c.1827A>G

Your query was ambiguous. Multiple possible variants found:

• chr9-2073292-A-G
• chr9-2073292-A-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.1827A>G​(p.Pro609Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 1,613,946 control chromosomes in the GnomAD database, including 11,436 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1215 hom., cov: 32)
  • Exomes 𝑓: 0.12 (10221 hom.)
• Consequence: SMARCA2 NM_003070.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.402
• Publications: 17 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=-0.47).
• BP6: Variant 9-2073292-A-G is Benign according to our data. Variant chr9-2073292-A-G is described in ClinVar as Benign. ClinVar VariationId is 126345.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.402 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.148 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.1827A>G	p.Pro609Pro	synonymous	Exon 11 of 34	NP_003061.3
	SMARCA2	NM_001289396.2		c.1827A>G	p.Pro609Pro	synonymous	Exon 11 of 34	NP_001276325.1	P51531-1
	SMARCA2	NM_139045.4		c.1827A>G	p.Pro609Pro	synonymous	Exon 11 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.1827A>G	p.Pro609Pro	synonymous	Exon 11 of 34	ENSP00000265773.5	P51531-1
	SMARCA2	ENST00000382203.5	TSL:1	c.1827A>G	p.Pro609Pro	synonymous	Exon 11 of 34	ENSP00000371638.1	P51531-1
	SMARCA2	ENST00000450198.6	TSL:1	c.1827A>G	p.Pro609Pro	synonymous	Exon 11 of 33	ENSP00000392081.2	F6VDE0

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18313 AN: 152094 Hom.: 1215 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.0706

Gnomad EAS AF: 0.0497

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.105

GnomAD2 exomes AF: 0.120 AC: 30078 AN: 251364 AF XY: 0.119

Gnomad AFR exome AF: 0.131

Gnomad AMR exome AF: 0.155

Gnomad ASJ exome AF: 0.0714

Gnomad EAS exome AF: 0.0509

Gnomad FIN exome AF: 0.148

Gnomad NFE exome AF: 0.113

Gnomad OTH exome AF: 0.112

GnomAD4 exome AF: 0.116 AC: 169809 AN: 1461734 Hom.: 10221 Cov.: 32 AF XY: 0.117 AC XY: 85006 AN XY: 727168

African (AFR) AF: 0.131 AC: 4372 AN: 33478

American (AMR) AF: 0.154 AC: 6866 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0723 AC: 1889 AN: 26130

East Asian (EAS) AF: 0.0498 AC: 1978 AN: 39700

South Asian (SAS) AF: 0.139 AC: 11965 AN: 86246

European-Finnish (FIN) AF: 0.149 AC: 7953 AN: 53418

Middle Eastern (MID) AF: 0.0830 AC: 479 AN: 5768

European-Non Finnish (NFE) AF: 0.115 AC: 127809 AN: 1111884

Other (OTH) AF: 0.108 AC: 6498 AN: 60394

GnomAD4 genome AF: 0.120 AC: 18326 AN: 152212 Hom.: 1215 Cov.: 32 AF XY: 0.123 AC XY: 9153 AN XY: 74422

African (AFR) AF: 0.129 AC: 5364 AN: 41536

American (AMR) AF: 0.154 AC: 2348 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0706 AC: 245 AN: 3470

East Asian (EAS) AF: 0.0498 AC: 258 AN: 5176

South Asian (SAS) AF: 0.125 AC: 605 AN: 4826

European-Finnish (FIN) AF: 0.148 AC: 1570 AN: 10582

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7638 AN: 68006

Other (OTH) AF: 0.103 AC: 217 AN: 2116

Alfa AF: 0.113 Hom.: 1898

Bravo AF: 0.120

Asia WGS AF: 0.0840 AC: 295 AN: 3478

EpiCase AF: 0.104

EpiControl AF: 0.103

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	-0.47
CADD	Benign	6.3
DANN	Benign	0.72
PhyloP100		-0.40
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: rs13288443; hg19: chr9-2073292; COSMIC: COSV100570667;