9-2039776-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG

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.696_707dupGCAGCAGCAGCA(p.Gln233_Gln236dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000983 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 INS_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. Q236Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00098 ( 0 hom., cov: 26)

Exomes 𝑓: 0.00070 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

SMARCA2
NM_003070.5 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.00

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-A-ACAGCAGCAGCAG is Benign according to our data. Variant chr9-2039776-A-ACAGCAGCAGCAG is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 588473.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000983 (148/150530) while in subpopulation SAS AF = 0.00446 (21/4712). AF 95% confidence interval is 0.00299. There are 0 homozygotes in GnomAd4. There are 83 alleles in the male GnomAd4 subpopulation. Median coverage is 26. This position passed quality control check.

BS2

High AC in GnomAd4 at 148 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
SMARCA2	NM_003070.5 link	c.696_707dupGCAGCAGCAGCA	p.Gln233_Gln236dup	disruptive_inframe_insertion	Exon 4 of 34	ENST00000349721.8	NP_003061.3
SMARCA2	NM_001289396.2 link	c.696_707dupGCAGCAGCAGCA	p.Gln233_Gln236dup	disruptive_inframe_insertion	Exon 4 of 34		NP_001276325.1
SMARCA2	NM_139045.4 link	c.696_707dupGCAGCAGCAGCA	p.Gln233_Gln236dup	disruptive_inframe_insertion	Exon 4 of 33		NP_620614.2
SMARCA2	NM_001289397.2 link	c.696_707dupGCAGCAGCAGCA	p.Gln233_Gln236dup	disruptive_inframe_insertion	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.696_707dupGCAGCAGCAGCA	p.Gln233_Gln236dup	disruptive_inframe_insertion	Exon 4 of 34	5	NM_003070.5	ENSP00000265773.5

Frequencies

GnomAD3 genomes

AF:

0.000990

AC:

149

AN:

150430

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00196

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00444

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000666

Gnomad OTH

AF:

0.000484

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000702

AC:

1015

AN:

1445598

Hom.:

Cov.:

AF XY:

0.000767

AC XY:

551

AN XY:

718472

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00162

AC:

AN:

32772

American (AMR)

AF:

0.000187

AC:

AN:

42718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25866

East Asian (EAS)

AF:

0.0000520

AC:

AN:

38448

South Asian (SAS)

AF:

0.00292

AC:

248

AN:

84892

European-Finnish (FIN)

AF:

0.0000967

AC:

AN:

51680

Middle Eastern (MID)

AF:

0.000180

AC:

AN:

5568

European-Non Finnish (NFE)

AF:

0.000602

AC:

665

AN:

1103952

Other (OTH)

AF:

0.000553

AC:

AN:

59702

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.360

Heterozygous variant carriers

131

175

219

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<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:

0.000983

AC:

148

AN:

150530

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

AN XY:

73484

show subpopulations

African (AFR)

AF:

0.00193

AC:

AN:

40906

American (AMR)

AF:

0.000132

AC:

AN:

15128

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5082

South Asian (SAS)

AF:

0.00446

AC:

AN:

4712

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10366

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000666

AC:

AN:

67586

Other (OTH)

AF:

0.000478

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

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:

0.00

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Apr 15, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

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

Inborn genetic diseases

Benign:1

Jun 20, 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

0.0

Mutation Taster

=86/14

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