rs146990134

Variant names:

• chr9-2029119-C-G
• NM_003070.5:c.97C>G

Your query was ambiguous. Multiple possible variants found:

• chr9-2029119-C-G
• chr9-2029119-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP2 BP4

The NM_003070.5(SMARCA2):​c.97C>G​(p.Pro33Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,453,332 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.06

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 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.
• BP4: Computational evidence support a benign effect (MetaRNN=0.42243502).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCA2	NM_003070.5	c.97C>G	p.Pro33Ala	missense_variant	Exon 2 of 34	ENST00000349721.8	NP_003061.3
SMARCA2	NM_001289396.2	c.97C>G	p.Pro33Ala	missense_variant	Exon 2 of 34		NP_001276325.1
SMARCA2	NM_139045.4	c.97C>G	p.Pro33Ala	missense_variant	Exon 2 of 33		NP_620614.2
SMARCA2	NM_001289397.2	c.97C>G	p.Pro33Ala	missense_variant	Exon 2 of 33		NP_001276326.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCA2	ENST00000349721.8	c.97C>G	p.Pro33Ala	missense_variant	Exon 2 of 34	5	NM_003070.5	ENSP00000265773.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1453332 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 722206

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: 0.00000181

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	Benign	0.073
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.060	.;.;T;T;T;T;T;.;T;T;T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.97	.;D;.;.;.;D;D;D;D;D;D
M_CAP	Uncertain	0.094	D
MetaRNN	Benign	0.42	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Uncertain	0.58	D
MutationAssessor	Benign	1.8	L;.;.;L;.;.;.;L;.;.;L
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.4	N;N;.;N;.;.;D;N;D;.;N
REVEL	Uncertain	0.36
Sift	Uncertain	0.015	D;D;.;D;.;.;D;D;D;.;D
Sift4G	Uncertain	0.021	D;D;.;D;.;.;T;D;T;.;D
Polyphen		1.0	D;.;.;D;.;.;.;D;.;.;D
Vest4		0.46
MutPred		0.16		Loss of glycosylation at P33 (P = 0.0133);Loss of glycosylation at P33 (P = 0.0133);Loss of glycosylation at P33 (P = 0.0133);Loss of glycosylation at P33 (P = 0.0133);Loss of glycosylation at P33 (P = 0.0133);Loss of glycosylation at P33 (P = 0.0133);Loss of glycosylation at P33 (P = 0.0133);Loss of glycosylation at P33 (P = 0.0133);Loss of glycosylation at P33 (P = 0.0133);Loss of glycosylation at P33 (P = 0.0133);Loss of glycosylation at P33 (P = 0.0133);
MVP		0.75
MPC		0.046
ClinPred		0.81	D
GERP RS		5.5
Varity_R		0.17
gMVP		0.13

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-2029119;