rs1112534

Variant names:

• chr9-2032845-G-A
• rs1112534
• NM_003070.5:c.226-107G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-2032845-G-A
• chr9-2032845-G-C
• chr9-2032845-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003070.5(SMARCA2):​c.226-107G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 974,010 control chromosomes in the GnomAD database, including 22,322 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4252 hom., cov: 32)
  • Exomes 𝑓: 0.20 (18070 hom.)
• Consequence: SMARCA2 NM_003070.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.372
• Publications: 8 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 9-2032845-G-A is Benign according to our data. Variant chr9-2032845-G-A is described in ClinVar as Benign. ClinVar VariationId is 1235432.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCA2	NM_003070.5	c.226-107G>A		intron_variant	Intron 2 of 33	ENST00000349721.8	NP_003061.3
SMARCA2	NM_001289396.2	c.226-107G>A		intron_variant	Intron 2 of 33		NP_001276325.1
SMARCA2	NM_139045.4	c.226-107G>A		intron_variant	Intron 2 of 32		NP_620614.2
SMARCA2	NM_001289397.2	c.226-107G>A		intron_variant	Intron 2 of 32		NP_001276326.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCA2	ENST00000349721.8	c.226-107G>A		intron_variant	Intron 2 of 33	5	NM_003070.5	ENSP00000265773.5

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34791 AN: 151992 Hom.: 4233 Cov.: 32

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.218

GnomAD4 exome AF: 0.204 AC: 167310 AN: 821900 Hom.: 18070 AF XY: 0.200 AC XY: 84187 AN XY: 420880

African (AFR) AF: 0.282 AC: 5482 AN: 19428

American (AMR) AF: 0.331 AC: 8395 AN: 25378

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 2468 AN: 16444

East Asian (EAS) AF: 0.335 AC: 11470 AN: 34252

South Asian (SAS) AF: 0.170 AC: 9345 AN: 55070

European-Finnish (FIN) AF: 0.214 AC: 9178 AN: 42814

Middle Eastern (MID) AF: 0.123 AC: 449 AN: 3646

European-Non Finnish (NFE) AF: 0.192 AC: 112865 AN: 586680

Other (OTH) AF: 0.201 AC: 7658 AN: 38188

GnomAD4 genome AF: 0.229 AC: 34846 AN: 152110 Hom.: 4252 Cov.: 32 AF XY: 0.232 AC XY: 17270 AN XY: 74378

African (AFR) AF: 0.279 AC: 11576 AN: 41496

American (AMR) AF: 0.309 AC: 4725 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 549 AN: 3468

East Asian (EAS) AF: 0.308 AC: 1590 AN: 5164

South Asian (SAS) AF: 0.196 AC: 946 AN: 4830

European-Finnish (FIN) AF: 0.214 AC: 2261 AN: 10554

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12654 AN: 67990

Other (OTH) AF: 0.224 AC: 473 AN: 2110

Alfa AF: 0.204 Hom.: 3481

Bravo AF: 0.238

Asia WGS AF: 0.287 AC: 999 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 03, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.1
DANN	Benign	0.36
PhyloP100		0.37
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: rs1112534; hg19: chr9-2032845; COSMIC: COSV104414050;