9-2028757-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_003070.5(SMARCA2):c.-36-230T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,218 control chromosomes in the GnomAD database, including 1,305 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.12 (1305 hom., cov: 32)
• Consequence: SMARCA2 NM_003070.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.19

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 9-2028757-T-G is Benign according to our data. Variant chr9-2028757-T-G is described in ClinVar as [Benign]. Clinvar id is 1231248.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMARCA2	NM_003070.5	c.-36-230T>G		intron_variant		ENST00000349721.8
SMARCA2	NM_001289396.1	c.-36-230T>G		intron_variant
SMARCA2	NM_001289397.2	c.-36-230T>G		intron_variant
SMARCA2	NM_139045.4	c.-36-230T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCA2	ENST00000349721.8	c.-36-230T>G		intron_variant		5	NM_003070.5	P2

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18847 AN: 152100 Hom.: 1297 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.0853

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.124 AC: 18880 AN: 152218 Hom.: 1305 Cov.: 32 AF XY: 0.126 AC XY: 9347 AN XY: 74428

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.0853

Gnomad4 EAS AF: 0.268

Gnomad4 SAS AF: 0.173

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.119

Alfa AF: 0.123 Hom.: 595

Bravo AF: 0.119

Asia WGS AF: 0.247 AC: 857 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
Cadd	Benign	19
Dann	Benign	0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs10964465; hg19: chr9-2028757;