NM_003070.5:c.50C>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2

The NM_003070.5(SMARCA2):​c.50C>A​(p.Pro17Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000141 in 1,415,106 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SMARCA2
NM_003070.5 missense

Scores

5
10
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.17
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in the SMARCA2 gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 93 curated pathogenic missense variants (we use a threshold of 10). The gene has 88 curated benign missense variants. Gene score misZ: 5.054 (above the threshold of 3.09). Trascript score misZ: 4.663 (above the threshold of 3.09). GenCC associations: The gene is linked to intellectual disability-sparse hair-brachydactyly syndrome, Coffin-Siris syndrome 1.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SMARCA2NM_003070.5 linkc.50C>A p.Pro17Gln missense_variant Exon 2 of 34 ENST00000349721.8 NP_003061.3 P51531-1Q8N9Q1Q56A76
SMARCA2NM_001289396.2 linkc.50C>A p.Pro17Gln missense_variant Exon 2 of 34 NP_001276325.1 P51531-1Q8N9Q1B4DSC8
SMARCA2NM_139045.4 linkc.50C>A p.Pro17Gln missense_variant Exon 2 of 33 NP_620614.2 P51531-2Q8N9Q1Q56A76
SMARCA2NM_001289397.2 linkc.50C>A p.Pro17Gln missense_variant Exon 2 of 33 NP_001276326.1 P51531F6VDE0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SMARCA2ENST00000349721.8 linkc.50C>A p.Pro17Gln missense_variant Exon 2 of 34 5 NM_003070.5 ENSP00000265773.5 P51531-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000141
AC:
2
AN:
1415106
Hom.:
0
Cov.:
32
AF XY:
0.00000143
AC XY:
1
AN XY:
699872
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000184
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.44
BayesDel_addAF
Pathogenic
0.20
D
BayesDel_noAF
Uncertain
0.050
CADD
Pathogenic
26
DANN
Uncertain
0.98
DEOGEN2
Benign
0.10
.;.;T;T;T;T;T;.;T;T;T
Eigen
Pathogenic
0.70
Eigen_PC
Pathogenic
0.70
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.95
.;D;.;.;.;D;D;D;D;D;D
M_CAP
Uncertain
0.15
D
MetaRNN
Uncertain
0.50
D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
0.64
D
MutationAssessor
Benign
1.8
L;.;.;L;.;.;.;L;.;.;L
PrimateAI
Pathogenic
0.88
D
PROVEAN
Benign
-2.3
N;D;.;N;.;.;D;N;D;.;N
REVEL
Uncertain
0.46
Sift
Pathogenic
0.0
D;D;.;D;.;.;D;D;D;.;D
Sift4G
Uncertain
0.047
D;D;.;D;.;.;D;D;D;.;D
Polyphen
1.0
D;.;.;D;.;.;.;D;.;.;D
Vest4
0.55
MutPred
0.18
Loss of glycosylation at P17 (P = 0.0309);Loss of glycosylation at P17 (P = 0.0309);Loss of glycosylation at P17 (P = 0.0309);Loss of glycosylation at P17 (P = 0.0309);Loss of glycosylation at P17 (P = 0.0309);Loss of glycosylation at P17 (P = 0.0309);Loss of glycosylation at P17 (P = 0.0309);Loss of glycosylation at P17 (P = 0.0309);Loss of glycosylation at P17 (P = 0.0309);Loss of glycosylation at P17 (P = 0.0309);Loss of glycosylation at P17 (P = 0.0309);
MVP
0.79
MPC
0.045
ClinPred
0.91
D
GERP RS
5.4
Varity_R
0.38
gMVP
0.26

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs543241889; hg19: chr9-2029072; API