9-2029072-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 1P and 12B. PP3BP6_Very_StrongBS2

The NM_003070.5(SMARCA2):c.50C>T(p.Pro17Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000191 in 1,567,482 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P17R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

SMARCA2
NM_003070.5 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 6.17

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

SMARCA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.826

BP6

Variant 9-2029072-C-T is Benign according to our data. Variant chr9-2029072-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1186796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 5 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	UniProt
SMARCA2	NM_003070.5	MANE Select	c.50C>T	p.Pro17Leu	missense	Exon 2 of 34	NP_003061.3
SMARCA2	NM_001289396.2		c.50C>T	p.Pro17Leu	missense	Exon 2 of 34	NP_001276325.1	P51531-1
SMARCA2	NM_139045.4		c.50C>T	p.Pro17Leu	missense	Exon 2 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.50C>T	p.Pro17Leu	missense	Exon 2 of 34	ENSP00000265773.5	P51531-1
SMARCA2	ENST00000382203.5	TSL:1	c.50C>T	p.Pro17Leu	missense	Exon 2 of 34	ENSP00000371638.1	P51531-1
SMARCA2	ENST00000450198.6	TSL:1	c.50C>T	p.Pro17Leu	missense	Exon 2 of 33	ENSP00000392081.2	F6VDE0

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152258

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000112

AC:

AN:

178370

AF XY:

0.0000104

show subpopulations

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:

0.0000139

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000177

AC:

AN:

1415106

Hom.:

Cov.:

AF XY:

0.0000157

AC XY:

AN XY:

699872

show subpopulations

African (AFR)

AF:

0.0000623

AC:

AN:

32110

American (AMR)

AF:

0.00

AC:

AN:

38436

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25366

East Asian (EAS)

AF:

0.00

AC:

AN:

36952

South Asian (SAS)

AF:

0.0000123

AC:

AN:

81232

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50240

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5442

European-Non Finnish (NFE)

AF:

0.0000193

AC:

AN:

1086800

Other (OTH)

AF:

0.0000171

AC:

AN:

58528

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152376

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74510

show subpopulations

African (AFR)

AF:

0.0000721

AC:

AN:

41598

American (AMR)

AF:

0.00

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68042

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.595

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.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000250

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Pathogenic

0.71

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.91

M_CAP

Uncertain

0.21

MetaRNN

Pathogenic

0.83

MetaSVM

Uncertain

0.69

MutationAssessor

Benign

1.8

PhyloP100

6.2

PrimateAI

Pathogenic

0.91

PROVEAN

Uncertain

-3.5

REVEL

Uncertain

0.54

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.012

Polyphen

1.0

Vest4

0.60

MVP

0.76

MPC

0.048

ClinPred

0.96

GERP RS

5.4

Varity_R

0.52

gMVP

0.20

Mutation Taster

=17/83

disease causing

(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

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

Computational scores

Splicing

Publications

Other links and lift over