Genetic Variant SMARCA2:p.Gln234_Gln236del (chr9-2039776-ACAGCAGCAG-A) – ACMG Classification: Benign (-17 pts)

Variant summary

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

The NM_003070.5(SMARCA2):c.699_707delGCAGCAGCA(p.Gln234_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 0.004 in 1,596,338 control chromosomes in the GnomAD database, including 11 homozygotes. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. Q233Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0053 ( 4 hom., cov: 26)

Exomes 𝑓: 0.0039 ( 7 hom. )

Consequence

SMARCA2
NM_003070.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 1.16

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-ACAGCAGCAG-A is Benign according to our data. Variant chr9-2039776-ACAGCAGCAG-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 212231.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00529 (797/150528) while in subpopulation AFR AF = 0.0105 (429/40904). AF 95% confidence interval is 0.00967. There are 4 homozygotes in GnomAd4. There are 381 alleles in the male GnomAd4 subpopulation. Median coverage is 26. This position passed quality control check.

BS2

High AC in GnomAd4 at 797 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003070.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SMARCA2	NM_003070.5	MANE Select	c.699_707delGCAGCAGCA	p.Gln234_Gln236del	disruptive_inframe_deletion	Exon 4 of 34	NP_003061.3
SMARCA2	NM_001289396.2		c.699_707delGCAGCAGCA	p.Gln234_Gln236del	disruptive_inframe_deletion	Exon 4 of 34	NP_001276325.1
SMARCA2	NM_139045.4		c.699_707delGCAGCAGCA	p.Gln234_Gln236del	disruptive_inframe_deletion	Exon 4 of 33	NP_620614.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SMARCA2	ENST00000349721.8	TSL:5 MANE Select	c.699_707delGCAGCAGCA	p.Gln234_Gln236del	disruptive_inframe_deletion	Exon 4 of 34	ENSP00000265773.5
SMARCA2	ENST00000382203.5	TSL:1	c.699_707delGCAGCAGCA	p.Gln234_Gln236del	disruptive_inframe_deletion	Exon 4 of 34	ENSP00000371638.1
SMARCA2	ENST00000450198.6	TSL:1	c.699_707delGCAGCAGCA	p.Gln234_Gln236del	disruptive_inframe_deletion	Exon 4 of 33	ENSP00000392081.2

Frequencies

GnomAD3 genomes

AF:

0.00530

AC:

798

AN:

150428

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0105

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00430

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00334

Gnomad SAS

AF:

0.00592

Gnomad FIN

AF:

0.000289

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.00360

Gnomad OTH

AF:

0.00532

GnomAD4 exome

AF:

0.00386

AC:

5586

AN:

1445810

Hom.:

AF XY:

0.00391

AC XY:

2813

AN XY:

718568

show subpopulations

African (AFR)

AF:

0.00994

AC:

326

AN:

32786

American (AMR)

AF:

0.00417

AC:

178

AN:

42718

Ashkenazi Jewish (ASJ)

AF:

0.000696

AC:

AN:

25866

East Asian (EAS)

AF:

0.00466

AC:

179

AN:

38446

South Asian (SAS)

AF:

0.00674

AC:

572

AN:

84908

European-Finnish (FIN)

AF:

0.000890

AC:

AN:

51678

Middle Eastern (MID)

AF:

0.00880

AC:

AN:

5568

European-Non Finnish (NFE)

AF:

0.00363

AC:

4010

AN:

1104138

Other (OTH)

AF:

0.00348

AC:

208

AN:

59702

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

369

739

1108

1478

1847

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

160

320

480

640

800

<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:

0.00529

AC:

797

AN:

150528

Hom.:

Cov.:

AF XY:

0.00518

AC XY:

381

AN XY:

73486

show subpopulations

African (AFR)

AF:

0.0105

AC:

429

AN:

40904

American (AMR)

AF:

0.00430

AC:

AN:

15128

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00335

AC:

AN:

5082

South Asian (SAS)

AF:

0.00594

AC:

AN:

4712

European-Finnish (FIN)

AF:

0.000289

AC:

AN:

10366

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00358

AC:

242

AN:

67586

Other (OTH)

AF:

0.00526

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

117

156

195

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:7

Mar 04, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Apr 13, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely 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

Sep 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SMARCA2: BS1, BS2

Feb 01, 2022

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

not specified

Benign:1

Oct 31, 2019

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Inborn genetic diseases

Benign:1

Sep 02, 2021

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.

Nicolaides-Baraitser syndrome

Benign:1

Jun 06, 2023

Molecular Genetics, Royal Melbourne Hospital

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.2

Mutation Taster

=177/23

polymorphism

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over