GeneBe

NM_003070.5:c.687_707dupGCAGCAGCAGCAGCAGCAGCA

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP3BS2

The NM_003070.5(SMARCA2):​c.687_707dupGCAGCAGCAGCAGCAGCAGCA​(p.Gln230_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 0.0000332 in 150,432 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q236Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 26)
Exomes 𝑓: 0.000018 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

SMARCA2
NM_003070.5 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP3
Nonframeshift variant in repetitive region in NM_003070.5
BS2
High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SMARCA2NM_003070.5 linkc.687_707dupGCAGCAGCAGCAGCAGCAGCA p.Gln230_Gln236dup disruptive_inframe_insertion Exon 4 of 34 ENST00000349721.8 NP_003061.3
SMARCA2NM_001289396.2 linkc.687_707dupGCAGCAGCAGCAGCAGCAGCA p.Gln230_Gln236dup disruptive_inframe_insertion Exon 4 of 34 NP_001276325.1
SMARCA2NM_139045.4 linkc.687_707dupGCAGCAGCAGCAGCAGCAGCA p.Gln230_Gln236dup disruptive_inframe_insertion Exon 4 of 33 NP_620614.2
SMARCA2NM_001289397.2 linkc.687_707dupGCAGCAGCAGCAGCAGCAGCA p.Gln230_Gln236dup disruptive_inframe_insertion Exon 4 of 33 NP_001276326.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SMARCA2ENST00000349721.8 linkc.687_707dupGCAGCAGCAGCAGCAGCAGCA p.Gln230_Gln236dup disruptive_inframe_insertion Exon 4 of 34 5 NM_003070.5 ENSP00000265773.5

Frequencies

GnomAD3 genomes
AF:
0.0000332
AC:
5
AN:
150432
Hom.:
0
Cov.:
26
show subpopulations
Gnomad AFR
AF:
0.0000245
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:
0.0000592
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000180
AC:
26
AN:
1445808
Hom.:
0
Cov.:
28
AF XY:
0.0000223
AC XY:
16
AN XY:
718560
show subpopulations
African (AFR)
AF:
0.0000305
AC:
1
AN:
32786
American (AMR)
AF:
0.0000234
AC:
1
AN:
42718
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25866
East Asian (EAS)
AF:
0.0000260
AC:
1
AN:
38448
South Asian (SAS)
AF:
0.0000236
AC:
2
AN:
84908
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
51680
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5568
European-Non Finnish (NFE)
AF:
0.0000181
AC:
20
AN:
1104128
Other (OTH)
AF:
0.0000167
AC:
1
AN:
59706
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.404
Heterozygous variant carriers
0
1
2
4
5
6
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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:
0.0000332
AC:
5
AN:
150432
Hom.:
0
Cov.:
26
AF XY:
0.0000409
AC XY:
3
AN XY:
73378
show subpopulations
African (AFR)
AF:
0.0000245
AC:
1
AN:
40792
American (AMR)
AF:
0.00
AC:
0
AN:
15108
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3462
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5096
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4728
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10366
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
0.0000592
AC:
4
AN:
67592
Other (OTH)
AF:
0.00
AC:
0
AN:
2068
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.465
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
0.0
Mutation Taster
=86/14
polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs113070757; hg19: chr9-2039776; API