dbSNP rs6601: SMARCA2:p.Glu1224Glu (chr9-2116037-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003070.5(SMARCA2):c.3672G>A(p.Glu1224Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,612,202 control chromosomes in the GnomAD database, including 22,628 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 7917 hom., cov: 32)

Exomes 𝑓: 0.12 ( 14711 hom. )

Consequence

SMARCA2
NM_003070.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.191

Publications

15 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: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Orphanet
blepharophimosis-impaired intellectual development syndrome
Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia

SMARCA2 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_003070.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 9-2116037-G-A is Benign according to our data. Variant chr9-2116037-G-A is described in ClinVar as Benign. ClinVar VariationId is 126346.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.191 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.586 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	UniProt
SMARCA2	NM_003070.5	MANE Select	c.3672G>A	p.Glu1224Glu	synonymous	Exon 25 of 34	NP_003061.3
SMARCA2	NM_001289396.2		c.3672G>A	p.Glu1224Glu	synonymous	Exon 25 of 34	NP_001276325.1	P51531-1
SMARCA2	NM_139045.4		c.3672G>A	p.Glu1224Glu	synonymous	Exon 25 of 33	NP_620614.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SMARCA2	ENST00000349721.8	TSL:5 MANE Select	c.3672G>A	p.Glu1224Glu	synonymous	Exon 25 of 34	ENSP00000265773.5	P51531-1
SMARCA2	ENST00000382203.5	TSL:1	c.3672G>A	p.Glu1224Glu	synonymous	Exon 25 of 34	ENSP00000371638.1	P51531-1
SMARCA2	ENST00000450198.6	TSL:1	c.3498G>A	p.Glu1166Glu	synonymous	Exon 25 of 33	ENSP00000392081.2	F6VDE0

Frequencies

GnomAD3 genomes

AF:

0.234

AC:

35534

AN:

151964

Hom.:

7872

Cov.:

show subpopulations

Gnomad AFR

AF:

0.592

Gnomad AMI

AF:

0.0932

Gnomad AMR

AF:

0.113

Gnomad ASJ

AF:

0.0798

Gnomad EAS

AF:

0.0194

Gnomad SAS

AF:

0.0926

Gnomad FIN

AF:

0.0873

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.105

Gnomad OTH

AF:

0.179

GnomAD2 exomes

AF:

0.123

AC:

30639

AN:

249844

AF XY:

0.115

show subpopulations

Gnomad AFR exome

AF:

0.606

Gnomad AMR exome

AF:

0.0649

Gnomad ASJ exome

AF:

0.0919

Gnomad EAS exome

AF:

0.0156

Gnomad FIN exome

AF:

0.0898

Gnomad NFE exome

AF:

0.105

Gnomad OTH exome

AF:

0.109

GnomAD4 exome

AF:

0.115

AC:

168002

AN:

1460120

Hom.:

14711

Cov.:

AF XY:

0.113

AC XY:

81859

AN XY:

726386

show subpopulations

African (AFR)

AF:

0.617

AC:

20602

AN:

33414

American (AMR)

AF:

0.0715

AC:

3195

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.0883

AC:

2306

AN:

26124

East Asian (EAS)

AF:

0.0300

AC:

1190

AN:

39682

South Asian (SAS)

AF:

0.0973

AC:

8383

AN:

86172

European-Finnish (FIN)

AF:

0.0916

AC:

4889

AN:

53356

Middle Eastern (MID)

AF:

0.140

AC:

806

AN:

5764

European-Non Finnish (NFE)

AF:

0.107

AC:

118607

AN:

1110570

Other (OTH)

AF:

0.133

AC:

8024

AN:

60342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

6826

13653

20479

27306

34132

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4556

9112

13668

18224

22780

<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:

0.234

AC:

35634

AN:

152082

Hom.:

7917

Cov.:

AF XY:

0.227

AC XY:

16874

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.593

AC:

24548

AN:

41430

American (AMR)

AF:

0.112

AC:

1717

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0798

AC:

277

AN:

3470

East Asian (EAS)

AF:

0.0195

AC:

101

AN:

5186

South Asian (SAS)

AF:

0.0931

AC:

448

AN:

4814

European-Finnish (FIN)

AF:

0.0873

AC:

925

AN:

10598

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.105

AC:

7113

AN:

67978

Other (OTH)

AF:

0.177

AC:

373

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1022

2043

3065

4086

5108

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

314

628

942

1256

1570

<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:

0.151

Hom.:

4177

Bravo

AF:

0.253

Asia WGS

AF:

0.0950

AC:

330

AN:

3478

EpiCase

AF:

0.108

EpiControl

AF:

0.106

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (2)

Inborn genetic diseases (1)

Nicolaides-Baraitser syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.74

(source)

DANN

Benign

0.41

PhyloP100

-0.19

Mutation Taster

=89/11

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

Computational scores

Splicing

Publications

Other links and lift over