Genetic Variant NM_001040142.2:c.-51-1751_-51-1735delAAAAAAAAAAAAAAAAA (chr2-165294010-TAAAAAAAAAAAAAAAAA-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001040142.2(SCN2A):c.-51-1751_-51-1735delAAAAAAAAAAAAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000315 in 95,122 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 0)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

SCN2A
NM_001040142.2 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.78

Publications

0 publications found

Variant links:

Genes affected

SCN2A (HGNC:10588): (sodium voltage-gated channel alpha subunit 2) Voltage-gated sodium channels are transmembrane glycoprotein complexes composed of a large alpha subunit with four repeat domains, each of which is composed of six membrane-spanning segments, and one or more regulatory beta subunits. Voltage-gated sodium channels function in the generation and propagation of action potentials in neurons and muscle. This gene encodes one member of the sodium channel alpha subunit gene family. Allelic variants of this gene are associated with seizure disorders and autism spectrum disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2016]

SCN2A Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen, Illumina
developmental and epileptic encephalopathy, 11
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
intellectual disability
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
episodic ataxia, type 9
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
seizures, benign familial infantile, 3
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
benign familial infantile epilepsy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
benign familial neonatal-infantile seizures
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Dravet syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
genetic developmental and epileptic encephalopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
infantile spasms
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
malignant migrating partial seizures of infancy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SCN2A links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN2A	NM_001040142.2 link	c.-51-1751_-51-1735delAAAAAAAAAAAAAAAAA		intron_variant	Intron 1 of 26	ENST00000375437.7	NP_001035232.1	Q99250-1
SCN2A	NM_001371246.1 link	c.-51-1751_-51-1735delAAAAAAAAAAAAAAAAA		intron_variant	Intron 1 of 26	ENST00000631182.3	NP_001358175.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SCN2A	ENST00000375437.7 link	c.-51-1762_-51-1746delAAAAAAAAAAAAAAAAA	intron_variant	Intron 1 of 26	5	NM_001040142.2	ENSP00000364586.2	Q99250-1
SCN2A	ENST00000631182.3 link	c.-51-1762_-51-1746delAAAAAAAAAAAAAAAAA	intron_variant	Intron 1 of 26	5	NM_001371246.1	ENSP00000486885.1	Q99250-2
SCN2A	ENST00000424833.5 link	c.-51-1762_-51-1746delAAAAAAAAAAAAAAAAA	intron_variant	Intron 1 of 10	1		ENSP00000406454.2	F6U291
SCN2A	ENST00000283256.10 link	c.-176_-160delAAAAAAAAAAAAAAAAA	upstream_gene_variant		1		ENSP00000283256.6	Q99250-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000315

AC:

AN:

95122

Hom.:

AF XY:

0.0000438

AC XY:

AN XY:

45646

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

2706

American (AMR)

AF:

0.00

AC:

AN:

160

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

748

East Asian (EAS)

AF:

0.00

AC:

AN:

444

South Asian (SAS)

AF:

0.00

AC:

AN:

2158

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.0000352

AC:

AN:

85206

Other (OTH)

AF:

0.00

AC:

AN:

3420

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.742

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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NM_001040142.2:c.-51-1751_-51-1735delAAAAAAAAAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over