Variant chr9-2029089-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP6_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

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.90

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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). GenCC has associacion of 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
SMARCA2	NM_003070.5 linkuse as main transcript	c.67C>T	p.Pro23Ser	missense_variant	2/34	ENST00000349721.8	NP_003061.3
SMARCA2	NM_001289396.1 linkuse as main transcript	c.67C>T	p.Pro23Ser	missense_variant	2/34		NP_001276325.1
SMARCA2	NM_139045.4 linkuse as main transcript	c.67C>T	p.Pro23Ser	missense_variant	2/33		NP_620614.2
SMARCA2	NM_001289397.2 linkuse as main transcript	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 linkuse as main transcript	c.67C>T	p.Pro23Ser	missense_variant	2/34	5	NM_003070.5	ENSP00000265773	P2	P51531-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

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

BayesDel_noAF

Uncertain

0.030

CADD

Uncertain

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

LIST_S2

Uncertain

0.96

.;D;.;.;.;D;D;D;D;D;D

M_CAP

Uncertain

0.11

MetaRNN

Uncertain

0.50

D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Uncertain

0.67

MutationAssessor

Benign

1.8

L;.;.;L;.;.;.;L;.;.;L

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.88

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over