Variant rs2304016 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001040142.2(SCN2A):c.971-32A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00512 in 1,537,156 control chromosomes in the GnomAD database, including 189 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.0058 ( 20 hom., cov: 32)

Exomes 𝑓: 0.0050 ( 169 hom. )

Consequence

SCN2A
NM_001040142.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.63

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but rather VUS (scored 4 / 10). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 2-165311993-A-G is Benign according to our data. Variant chr2-165311993-A-G is described in ClinVar as [Benign]. Clinvar id is 1257386.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-165311993-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN2A	NM_001040142.2 link	c.971-32A>G		intron_variant	Intron 7 of 26	ENST00000375437.7	NP_001035232.1	Q99250-1
SCN2A	NM_001371246.1 link	c.971-32A>G		intron_variant	Intron 7 of 26	ENST00000631182.3	NP_001358175.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SCN2A	ENST00000375437.7 link	c.971-32A>G	intron_variant	Intron 7 of 26	5	NM_001040142.2	ENSP00000364586.2	Q99250-1
SCN2A	ENST00000631182.3 link	c.971-32A>G	intron_variant	Intron 7 of 26	5	NM_001371246.1	ENSP00000486885.1	Q99250-2
SCN2A	ENST00000283256.10 link	c.971-32A>G	intron_variant	Intron 7 of 26	1		ENSP00000283256.6	Q99250-1
SCN2A	ENST00000424833.5 link	c.971-32A>G	intron_variant	Intron 7 of 10	1		ENSP00000406454.2	F6U291

Frequencies

GnomAD3 genomes

AF:

0.00584

AC:

888

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00891

Gnomad ASJ

AF:

0.0118

Gnomad EAS

AF:

0.0898

Gnomad SAS

AF:

0.00704

Gnomad FIN

AF:

0.00922

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00134

Gnomad OTH

AF:

0.00528

GnomAD3 exomes

AF:

0.0119

AC:

2907

AN:

244650

Hom.:

AF XY:

0.0108

AC XY:

1423

AN XY:

132278

show subpopulations

Gnomad AFR exome

AF:

0.000376

Gnomad AMR exome

AF:

0.0184

Gnomad ASJ exome

AF:

0.00925

Gnomad EAS exome

AF:

0.0897

Gnomad SAS exome

AF:

0.00470

Gnomad FIN exome

AF:

0.00816

Gnomad NFE exome

AF:

0.00200

Gnomad OTH exome

AF:

0.00653

GnomAD4 exome

AF:

0.00505

AC:

6990

AN:

1384906

Hom.:

169

Cov.:

AF XY:

0.00505

AC XY:

3501

AN XY:

693192

show subpopulations

Gnomad4 AFR exome

AF:

0.000219

Gnomad4 AMR exome

AF:

0.0180

Gnomad4 ASJ exome

AF:

0.00959

Gnomad4 EAS exome

AF:

0.0884

Gnomad4 SAS exome

AF:

0.00441

Gnomad4 FIN exome

AF:

0.00744

Gnomad4 NFE exome

AF:

0.00131

Gnomad4 OTH exome

AF:

0.00573

GnomAD4 genome

AF:

0.00581

AC:

884

AN:

152250

Hom.:

Cov.:

AF XY:

0.00705

AC XY:

525

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.00890

Gnomad4 ASJ

AF:

0.0118

Gnomad4 EAS

AF:

0.0893

Gnomad4 SAS

AF:

0.00684

Gnomad4 FIN

AF:

0.00922

Gnomad4 NFE

AF:

0.00134

Gnomad4 OTH

AF:

0.00522

Alfa

AF:

0.00235

Hom.:

Bravo

AF:

0.00651

Asia WGS

AF:

0.0430

AC:

149

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 28, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.84

La Branchor

0.80

BranchPoint Hunter

4.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

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