9-2039776-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAGCAGCAGCAGCAG

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBA1

The NM_003070.5(SMARCA2):c.705_707delGCA(p.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 0.146 in 1,427,642 control chromosomes in the GnomAD database, including 5,709 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2394 hom., cov: 26)

Exomes 𝑓: 0.14 ( 3315 hom. )

Consequence

SMARCA2
NM_003070.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

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-ACAG-A is Benign according to our data. Variant chr9-2039776-ACAG-A is described in ClinVar as Benign. ClinVar VariationId is 126353.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

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.705_707delGCA	p.Gln236del	disruptive_inframe_deletion	Exon 4 of 34	NP_003061.3
SMARCA2	NM_001289396.2		c.705_707delGCA	p.Gln236del	disruptive_inframe_deletion	Exon 4 of 34	NP_001276325.1
SMARCA2	NM_139045.4		c.705_707delGCA	p.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.705_707delGCA	p.Gln236del	disruptive_inframe_deletion	Exon 4 of 34	ENSP00000265773.5
SMARCA2	ENST00000382203.5	TSL:1	c.705_707delGCA	p.Gln236del	disruptive_inframe_deletion	Exon 4 of 34	ENSP00000371638.1
SMARCA2	ENST00000450198.6	TSL:1	c.705_707delGCA	p.Gln236del	disruptive_inframe_deletion	Exon 4 of 33	ENSP00000392081.2

Frequencies

GnomAD3 genomes

AF:

0.165

AC:

24790

AN:

150198

Hom.:

2377

Cov.:

show subpopulations

Gnomad AFR

AF:

0.237

Gnomad AMI

AF:

0.0375

Gnomad AMR

AF:

0.142

Gnomad ASJ

AF:

0.0833

Gnomad EAS

AF:

0.365

Gnomad SAS

AF:

0.183

Gnomad FIN

AF:

0.162

Gnomad MID

AF:

0.0865

Gnomad NFE

AF:

0.118

Gnomad OTH

AF:

0.143

GnomAD4 exome

AF:

0.143

AC:

183010

AN:

1277344

Hom.:

3315

AF XY:

0.144

AC XY:

90470

AN XY:

627376

show subpopulations

African (AFR)

AF:

0.233

AC:

7052

AN:

30264

American (AMR)

AF:

0.207

AC:

7439

AN:

35932

Ashkenazi Jewish (ASJ)

AF:

0.0978

AC:

1997

AN:

20410

East Asian (EAS)

AF:

0.354

AC:

11364

AN:

32122

South Asian (SAS)

AF:

0.183

AC:

12195

AN:

66666

European-Finnish (FIN)

AF:

0.192

AC:

8255

AN:

42888

Middle Eastern (MID)

AF:

0.0889

AC:

426

AN:

4794

European-Non Finnish (NFE)

AF:

0.127

AC:

126434

AN:

993810

Other (OTH)

AF:

0.156

AC:

7848

AN:

50458

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

12023

24047

36070

48094

60117

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5042

10084

15126

20168

25210

<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:

0.165

AC:

24843

AN:

150298

Hom.:

2394

Cov.:

AF XY:

0.168

AC XY:

12320

AN XY:

73378

show subpopulations

African (AFR)

AF:

0.238

AC:

9714

AN:

40866

American (AMR)

AF:

0.143

AC:

2152

AN:

15100

Ashkenazi Jewish (ASJ)

AF:

0.0833

AC:

288

AN:

3458

East Asian (EAS)

AF:

0.365

AC:

1852

AN:

5080

South Asian (SAS)

AF:

0.183

AC:

860

AN:

4710

European-Finnish (FIN)

AF:

0.162

AC:

1669

AN:

10288

Middle Eastern (MID)

AF:

0.0793

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.118

AC:

7946

AN:

67510

Other (OTH)

AF:

0.146

AC:

305

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

939

1878

2818

3757

4696

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

270

540

810

1080

1350

<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:

0.106

Hom.:

Bravo

AF:

0.173

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Oct 24, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:2

Aug 12, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jan 13, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Inborn genetic diseases

Benign:1

Dec 16, 2022

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as 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;C5443984:Blepharophimosis-impaired intellectual development syndrome

Benign:1

Mar 30, 2022

Fulgent Genetics, Fulgent Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.0

Mutation Taster

=79/21

polymorphism (auto)

(source)

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

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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