9-2039776-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAGCAGCAGCAG

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_003070.5(SMARCA2):c.702_707del(p.Gln237_Gln238del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000621 in 1,575,304 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. Q223Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00089 (0 hom., cov: 26)
  • Exomes 𝑓: 0.00059 (0 hom.)
• Consequence: SMARCA2 NM_003070.5 inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.805

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 -16 ACMG points.

• BP6: Variant 9-2039776-ACAGCAG-A is Benign according to our data. Variant chr9-2039776-ACAGCAG-A is described in ClinVar as [Likely_benign]. Clinvar id is 587879.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-2039776-ACAGCAG-A is described in Lovd as [Likely_benign]. Variant chr9-2039776-ACAGCAG-A is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00089 (134/150500) while in subpopulation EAS AF= 0.00551 (28/5080). AF 95% confidence interval is 0.00392. There are 0 homozygotes in gnomad4. There are 59 alleles in male gnomad4 subpopulation. Median coverage is 26. This position pass quality control queck.
• BS2: High AC in GnomAd at 133 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMARCA2	NM_003070.5	c.702_707del	p.Gln237_Gln238del	inframe_deletion	4/34	ENST00000349721.8
SMARCA2	NM_001289396.1	c.702_707del	p.Gln237_Gln238del	inframe_deletion	4/34
SMARCA2	NM_001289397.2	c.702_707del	p.Gln237_Gln238del	inframe_deletion	4/33
SMARCA2	NM_139045.4	c.702_707del	p.Gln237_Gln238del	inframe_deletion	4/33

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCA2	ENST00000349721.8	c.702_707del	p.Gln237_Gln238del	inframe_deletion	4/34	5	NM_003070.5	P2

Frequencies

GnomAD3 genomes AF: 0.000884 AC: 133 AN: 150402 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.00199

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000199

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00550

Gnomad SAS AF: 0.000635

Gnomad FIN AF: 0.000193

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000207

Gnomad OTH AF: 0.000968

GnomAD4 exome AF: 0.000593 AC: 845 AN: 1424804 Hom.: 0 AF XY: 0.000539 AC XY: 382 AN XY: 708096

Gnomad4 AFR exome AF: 0.00314

Gnomad4 AMR exome AF: 0.00176

Gnomad4 ASJ exome AF: 0.00113

Gnomad4 EAS exome AF: 0.00677

Gnomad4 SAS exome AF: 0.000651

Gnomad4 FIN exome AF: 0.000828

Gnomad4 NFE exome AF: 0.000243

Gnomad4 OTH exome AF: 0.000680

GnomAD4 genome AF: 0.000890 AC: 134 AN: 150500 Hom.: 0 Cov.: 26 AF XY: 0.000803 AC XY: 59 AN XY: 73470

Gnomad4 AFR AF: 0.00200

Gnomad4 AMR AF: 0.000198

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00551

Gnomad4 SAS AF: 0.000637

Gnomad4 FIN AF: 0.000193

Gnomad4 NFE AF: 0.000207

Gnomad4 OTH AF: 0.000958

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

Inborn genetic diseases Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 04, 2018

This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2023

SMARCA2: BS1 -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs113070757; hg19: chr9-2039776;