9-2123639-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003070.5(SMARCA2):c.3763-80T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 1,244,436 control chromosomes in the GnomAD database, including 26,125 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (6317 hom., cov: 32)
  • Exomes 𝑓: 0.16 (19808 hom.)
• Consequence: SMARCA2 NM_003070.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.831

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 9-2123639-T-C is Benign according to our data. Variant chr9-2123639-T-C is described in ClinVar as [Benign]. Clinvar id is 1259756.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMARCA2	NM_003070.5	c.3763-80T>C		intron_variant		ENST00000349721.8
SMARCA2	NM_001289396.1	c.3763-80T>C		intron_variant
SMARCA2	NM_001289397.2	c.3589-80T>C		intron_variant
SMARCA2	NM_139045.4	c.3763-80T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCA2	ENST00000349721.8	c.3763-80T>C		intron_variant		5	NM_003070.5	P2

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36771 AN: 151816 Hom.: 6293 Cov.: 32

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.212

GnomAD4 exome AF: 0.157 AC: 171064 AN: 1092502 Hom.: 19808 AF XY: 0.158 AC XY: 87595 AN XY: 555860

Gnomad4 AFR exome AF: 0.464

Gnomad4 AMR exome AF: 0.258

Gnomad4 ASJ exome AF: 0.109

Gnomad4 EAS exome AF: 0.580

Gnomad4 SAS exome AF: 0.232

Gnomad4 FIN exome AF: 0.175

Gnomad4 NFE exome AF: 0.114

Gnomad4 OTH exome AF: 0.172

GnomAD4 genome AF: 0.242 AC: 36842 AN: 151934 Hom.: 6317 Cov.: 32 AF XY: 0.247 AC XY: 18317 AN XY: 74258

Gnomad4 AFR AF: 0.458

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.546

Gnomad4 SAS AF: 0.249

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.211

Alfa AF: 0.149 Hom.: 3058

Bravo AF: 0.256

Asia WGS AF: 0.375 AC: 1306 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	-0.82
Cadd	Benign	0.11
Dann	Benign	0.66

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: rs3829070; hg19: chr9-2123639; COSMIC: COSV61806288; COSMIC: COSV61806288;