Variant 9-2039776-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6

The NM_003070.5(SMARCA2):c.690_707dup(p.Gln233_Gln238dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000199 in 150,432 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. Q222Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 26)

Exomes 𝑓: 0.000075 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SMARCA2
NM_003070.5 inframe_insertion

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.00

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:

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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;

BP6

Variant 9-2039776-A-ACAGCAGCAGCAGCAGCAG is Benign according to our data. Variant chr9-2039776-A-ACAGCAGCAGCAGCAGCAG is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 126352.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SMARCA2	NM_003070.5 linkuse as main transcript	c.690_707dup	p.Gln233_Gln238dup	inframe_insertion	4/34	ENST00000349721.8	NP_003061.3
SMARCA2	NM_001289396.1 linkuse as main transcript	c.690_707dup	p.Gln233_Gln238dup	inframe_insertion	4/34		NP_001276325.1
SMARCA2	NM_001289397.2 linkuse as main transcript	c.690_707dup	p.Gln233_Gln238dup	inframe_insertion	4/33		NP_001276326.1
SMARCA2	NM_139045.4 linkuse as main transcript	c.690_707dup	p.Gln233_Gln238dup	inframe_insertion	4/33		NP_620614.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMARCA2	ENST00000349721.8 linkuse as main transcript	c.690_707dup	p.Gln233_Gln238dup	inframe_insertion	4/34	5	NM_003070.5	ENSP00000265773	P2	P51531-1

Frequencies

GnomAD3 genomes

AF:

0.0000199

AC:

AN:

150432

Hom.:

Cov.:

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:

0.0000965

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000747

AC:

108

AN:

1445768

Hom.:

Cov.:

AF XY:

0.0000710

AC XY:

AN XY:

718546

show subpopulations

Gnomad4 AFR exome

AF:

0.0000305

Gnomad4 AMR exome

AF:

0.0000936

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000156

Gnomad4 SAS exome

AF:

0.0000707

Gnomad4 FIN exome

AF:

0.0000580

Gnomad4 NFE exome

AF:

0.0000761

Gnomad4 OTH exome

AF:

0.0000670

GnomAD4 genome

AF:

0.0000199

AC:

AN:

150432

Hom.:

Cov.:

AF XY:

0.0000409

AC XY:

AN XY:

73378

show subpopulations

Gnomad4 AFR

AF:

0.0000245

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000965

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Coffin Siris/Intellectual Disability

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Feb 14, 2014

- -

Nicolaides-Baraitser syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Institute of Human Genetics, University of Leipzig Medical Center

Jan 01, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over