9-2076174-A-T

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.1936-55A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 968,268 control chromosomes in the GnomAD database, including 5,956 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.094 (800 hom., cov: 32)
  • Exomes 𝑓: 0.10 (5156 hom.)
• Consequence: SMARCA2 NM_003070.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.619

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=-0.81).
• BP6: Variant 9-2076174-A-T is Benign according to our data. Variant chr9-2076174-A-T is described in ClinVar as [Benign]. Clinvar id is 1270525.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMARCA2	NM_003070.5	c.1936-55A>T		intron_variant		ENST00000349721.8
SMARCA2	NM_001289396.1	c.1936-55A>T		intron_variant
SMARCA2	NM_001289397.2	c.1936-55A>T		intron_variant
SMARCA2	NM_139045.4	c.1936-55A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCA2	ENST00000349721.8	c.1936-55A>T		intron_variant		5	NM_003070.5	P2

Frequencies

GnomAD3 genomes AF: 0.0937 AC: 14250 AN: 152078 Hom.: 795 Cov.: 32

Gnomad AFR AF: 0.0582

Gnomad AMI AF: 0.0462

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0874

Gnomad OTH AF: 0.106

GnomAD4 exome AF: 0.103 AC: 83770 AN: 816072 Hom.: 5156 AF XY: 0.101 AC XY: 43498 AN XY: 431776

Gnomad4 AFR exome AF: 0.0591

Gnomad4 AMR exome AF: 0.179

Gnomad4 ASJ exome AF: 0.0922

Gnomad4 EAS exome AF: 0.267

Gnomad4 SAS exome AF: 0.0975

Gnomad4 FIN exome AF: 0.105

Gnomad4 NFE exome AF: 0.0886

Gnomad4 OTH exome AF: 0.105

GnomAD4 genome AF: 0.0938 AC: 14272 AN: 152196 Hom.: 800 Cov.: 32 AF XY: 0.0968 AC XY: 7206 AN XY: 74418

Gnomad4 AFR AF: 0.0581

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.276

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.0874

Gnomad4 OTH AF: 0.109

Alfa AF: 0.0289 Hom.: 24

Bravo AF: 0.0966

Asia WGS AF: 0.229 AC: 794 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	-0.81
Cadd	Benign	0.35
Dann	Benign	0.76

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: rs3763627; hg19: chr9-2076174; COSMIC: COSV61813146; COSMIC: COSV61813146;