9-2029089-C-T

Position:

• chr9-2029089-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP6_Moderate

The NM_003070.5(SMARCA2):​c.67C>T​(p.Pro23Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SMARCA2 NM_003070.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.90

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), SMARCA2. . Gene score misZ: 5.054 (greater than the threshold 3.09). Trascript score misZ: 4.663 (greater than threshold 3.09). The gene has 93 curated pathogenic missense variants (we use a threshold of 10). The gene has 88 curated benign missense variants. GenCC has associacion of the gene with intellectual disability-sparse hair-brachydactyly syndrome, Coffin-Siris syndrome 1.
• BP6: Variant 9-2029089-C-T is Benign according to our data. Variant chr9-2029089-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2429808.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMARCA2	NM_003070.5	c.67C>T	p.Pro23Ser	missense_variant	2/34	ENST00000349721.8	NP_003061.3
SMARCA2	NM_001289396.2	c.67C>T	p.Pro23Ser	missense_variant	2/34		NP_001276325.1
SMARCA2	NM_139045.4	c.67C>T	p.Pro23Ser	missense_variant	2/33		NP_620614.2
SMARCA2	NM_001289397.2	c.67C>T	p.Pro23Ser	missense_variant	2/33		NP_001276326.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMARCA2	ENST00000349721.8	c.67C>T	p.Pro23Ser	missense_variant	2/34	5	NM_003070.5	ENSP00000265773.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Autism spectrum disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Department of Genetics, Rouen University Hospital, Normandy Center for Genomic and Personalized Medicine

Apr 13, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	.;.;T;T;T;T;T;.;T;T;T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	.;D;.;.;.;D;D;D;D;D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.50	D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.67	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	0.50
Sift	Benign	0.045	D;D;.;D;.;.;D;D;D;.;D
Sift4G	Uncertain	0.027	D;D;.;D;.;.;D;D;D;.;D
Polyphen		1.0	D;.;.;D;.;.;.;D;.;.;D
Vest4		0.55
MutPred		0.22		Gain of phosphorylation at P23 (P = 0.0021);Gain of phosphorylation at P23 (P = 0.0021);Gain of phosphorylation at P23 (P = 0.0021);Gain of phosphorylation at P23 (P = 0.0021);Gain of phosphorylation at P23 (P = 0.0021);Gain of phosphorylation at P23 (P = 0.0021);Gain of phosphorylation at P23 (P = 0.0021);Gain of phosphorylation at P23 (P = 0.0021);Gain of phosphorylation at P23 (P = 0.0021);Gain of phosphorylation at P23 (P = 0.0021);Gain of phosphorylation at P23 (P = 0.0021);
MVP		0.81
MPC		0.048
ClinPred		0.72	D
GERP RS		5.5
Varity_R		0.20
gMVP		0.22

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: chr9-2029089;