9-2029030-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_003070.5(SMARCA2):c.8C>T(p.Thr3Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000774 in 1,549,584 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. T3T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000057 ( 0 hom. )

Consequence

SMARCA2
NM_003070.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.79

Publications

0 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: Likely_benign. The variant received -6 ACMG points.

BP6

Variant 9-2029030-C-T is Benign according to our data. Variant chr9-2029030-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2240617.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCA2	NM_003070.5 link	c.8C>T	p.Thr3Met	missense_variant	Exon 2 of 34	ENST00000349721.8	NP_003061.3	P51531-1Q8N9Q1Q56A76
SMARCA2	NM_001289396.2 link	c.8C>T	p.Thr3Met	missense_variant	Exon 2 of 34		NP_001276325.1	P51531-1Q8N9Q1B4DSC8
SMARCA2	NM_139045.4 link	c.8C>T	p.Thr3Met	missense_variant	Exon 2 of 33		NP_620614.2	P51531-2Q8N9Q1Q56A76
SMARCA2	NM_001289397.2 link	c.8C>T	p.Thr3Met	missense_variant	Exon 2 of 33		NP_001276326.1	P51531F6VDE0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCA2	ENST00000349721.8 link	c.8C>T	p.Thr3Met	missense_variant	Exon 2 of 34	5	NM_003070.5	ENSP00000265773.5		P51531-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

151316

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000573

AC:

AN:

1397328

Hom.:

Cov.:

AF XY:

0.00000725

AC XY:

AN XY:

689434

show subpopulations

African (AFR)

AF:

0.0000636

AC:

AN:

31454

American (AMR)

AF:

0.00

AC:

AN:

35080

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25088

East Asian (EAS)

AF:

0.00

AC:

AN:

35796

South Asian (SAS)

AF:

0.0000126

AC:

AN:

79320

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48966

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4656

European-Non Finnish (NFE)

AF:

0.00000278

AC:

AN:

1079096

Other (OTH)

AF:

0.0000346

AC:

AN:

57872

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152256

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.0000723

AC:

AN:

41470

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68046

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000264

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Aug 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Uncertain

0.13

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.058

.;.;.;T;T;T;T;.;.;T;.;T;T;.;T

Eigen

Uncertain

0.68

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.96

.;.;D;.;.;.;D;.;.;D;D;D;D;.;D

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.38

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Uncertain

0.77

MutationAssessor

Benign

1.8

.;L;.;.;L;.;.;.;.;.;L;.;.;.;L

PhyloP100

3.8

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-1.1

.;N;N;.;N;.;.;.;.;D;N;D;.;.;N

REVEL

Uncertain

0.49

Sift

Uncertain

0.0030

.;D;D;.;D;.;.;.;.;D;D;D;.;.;D

Sift4G

Uncertain

0.0090

.;D;D;.;D;.;.;.;.;D;D;D;.;.;D

Polyphen

1.0

.;D;.;.;D;.;.;.;.;.;D;.;.;.;D

Vest4

0.50, 0.51, 0.47, 0.47, 0.50

MutPred

0.17

Loss of phosphorylation at T3 (P = 0.0037);Loss of phosphorylation at T3 (P = 0.0037);Loss of phosphorylation at T3 (P = 0.0037);Loss of phosphorylation at T3 (P = 0.0037);Loss of phosphorylation at T3 (P = 0.0037);Loss of phosphorylation at T3 (P = 0.0037);Loss of phosphorylation at T3 (P = 0.0037);Loss of phosphorylation at T3 (P = 0.0037);Loss of phosphorylation at T3 (P = 0.0037);Loss of phosphorylation at T3 (P = 0.0037);Loss of phosphorylation at T3 (P = 0.0037);Loss of phosphorylation at T3 (P = 0.0037);Loss of phosphorylation at T3 (P = 0.0037);Loss of phosphorylation at T3 (P = 0.0037);Loss of phosphorylation at T3 (P = 0.0037);

MVP

0.79

MPC

0.049

ClinPred

0.87

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.28

gMVP

0.082

Mutation Taster

=41/59

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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.

9-2029030-C-T

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