9-2039776-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAG

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBS1BS2

The NM_003070.5(SMARCA2):c.693_707delGCAGCAGCAGCAGCA(p.Gln232_Gln236del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00351 in 150,530 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. Q231Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0035 ( 0 hom., cov: 26)

Exomes 𝑓: 0.0047 ( 12 hom. )

Failed GnomAD Quality Control

Consequence

SMARCA2
NM_003070.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 1.94

Publications

9 publications found

Variant links:

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

SMARCA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_003070.5

BP6

Variant 9-2039776-ACAGCAGCAGCAGCAG-A is Benign according to our data. Variant chr9-2039776-ACAGCAGCAGCAGCAG-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 212230.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00351 (528/150530) while in subpopulation NFE AF = 0.00491 (332/67584). AF 95% confidence interval is 0.00448. There are 0 homozygotes in GnomAd4. There are 231 alleles in the male GnomAd4 subpopulation. Median coverage is 26. This position passed quality control check.

BS2

High AC in GnomAd4 at 528 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
SMARCA2	NM_003070.5 link	c.693_707delGCAGCAGCAGCAGCA	p.Gln232_Gln236del	disruptive_inframe_deletion	Exon 4 of 34	ENST00000349721.8	NP_003061.3
SMARCA2	NM_001289396.2 link	c.693_707delGCAGCAGCAGCAGCA	p.Gln232_Gln236del	disruptive_inframe_deletion	Exon 4 of 34		NP_001276325.1
SMARCA2	NM_139045.4 link	c.693_707delGCAGCAGCAGCAGCA	p.Gln232_Gln236del	disruptive_inframe_deletion	Exon 4 of 33		NP_620614.2
SMARCA2	NM_001289397.2 link	c.693_707delGCAGCAGCAGCAGCA	p.Gln232_Gln236del	disruptive_inframe_deletion	Exon 4 of 33		NP_001276326.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCA2	ENST00000349721.8 link	c.693_707delGCAGCAGCAGCAGCA	p.Gln232_Gln236del	disruptive_inframe_deletion	Exon 4 of 34	5	NM_003070.5	ENSP00000265773.5

Frequencies

GnomAD3 genomes

AF:

0.00351

AC:

528

AN:

150430

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000981

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00351

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.000981

Gnomad SAS

AF:

0.000212

Gnomad FIN

AF:

0.00482

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00491

Gnomad OTH

AF:

0.00532

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00468

AC:

6760

AN:

1445818

Hom.:

AF XY:

0.00452

AC XY:

3246

AN XY:

718570

show subpopulations

African (AFR)

AF:

0.00119

AC:

AN:

32786

American (AMR)

AF:

0.00302

AC:

129

AN:

42718

Ashkenazi Jewish (ASJ)

AF:

0.0116

AC:

300

AN:

25866

East Asian (EAS)

AF:

0.000130

AC:

AN:

38448

South Asian (SAS)

AF:

0.000212

AC:

AN:

84908

European-Finnish (FIN)

AF:

0.00559

AC:

289

AN:

51680

Middle Eastern (MID)

AF:

0.00287

AC:

AN:

5568

European-Non Finnish (NFE)

AF:

0.00517

AC:

5710

AN:

1104138

Other (OTH)

AF:

0.00425

AC:

254

AN:

59706

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

436

872

1308

1744

2180

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

216

432

648

864

1080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00351

AC:

528

AN:

150530

Hom.:

Cov.:

AF XY:

0.00314

AC XY:

231

AN XY:

73486

show subpopulations

African (AFR)

AF:

0.000978

AC:

AN:

40908

American (AMR)

AF:

0.00350

AC:

AN:

15128

Ashkenazi Jewish (ASJ)

AF:

0.0104

AC:

AN:

3462

East Asian (EAS)

AF:

0.000984

AC:

AN:

5082

South Asian (SAS)

AF:

0.000212

AC:

AN:

4712

European-Finnish (FIN)

AF:

0.00482

AC:

AN:

10366

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00491

AC:

332

AN:

67584

Other (OTH)

AF:

0.00526

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

122

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00329

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:6

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Oct 22, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Nov 05, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Aug 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SMARCA2: BS1, BS2

Aug 29, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:2

Jul 24, 2015

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Inborn genetic diseases

Benign:1

Oct 07, 2018

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.9

Mutation Taster

=182/18

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over