rs1867864

Positions:

chr2-165323140-C-T

Variant summary

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

The NM_001040142.2(SCN2A):c.1672-16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 1,609,910 control chromosomes in the GnomAD database, including 254,998 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.56 ( 23906 hom., cov: 31)

Exomes 𝑓: 0.56 ( 231092 hom. )

Consequence

SCN2A
NM_001040142.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.303

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 2-165323140-C-T is Benign according to our data. Variant chr2-165323140-C-T is described in ClinVar as [Benign]. Clinvar id is 261400.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-165323140-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN2A	NM_001040142.2 link	c.1672-16C>T		intron_variant		ENST00000375437.7	NP_001035232.1	Q99250-1
SCN2A	NM_001371246.1 link	c.1672-16C>T		intron_variant		ENST00000631182.3	NP_001358175.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
SCN2A	ENST00000375437.7 link	c.1672-16C>T	intron_variant	5	NM_001040142.2	ENSP00000364586.2	Q99250-1
SCN2A	ENST00000631182.3 link	c.1672-16C>T	intron_variant	5	NM_001371246.1	ENSP00000486885.1	Q99250-2
SCN2A	ENST00000283256.10 link	c.1672-16C>T	intron_variant	1		ENSP00000283256.6	Q99250-1

Frequencies

GnomAD3 genomes

AF:

0.556

AC:

84378

AN:

151820

Hom.:

23895

Cov.:

show subpopulations

Gnomad AFR

AF:

0.610

Gnomad AMI

AF:

0.413

Gnomad AMR

AF:

0.490

Gnomad ASJ

AF:

0.624

Gnomad EAS

AF:

0.336

Gnomad SAS

AF:

0.492

Gnomad FIN

AF:

0.437

Gnomad MID

AF:

0.649

Gnomad NFE

AF:

0.575

Gnomad OTH

AF:

0.561

GnomAD3 exomes

AF:

0.512

AC:

126984

AN:

247808

Hom.:

33555

AF XY:

0.516

AC XY:

69331

AN XY:

134366

show subpopulations

Gnomad AFR exome

AF:

0.615

Gnomad AMR exome

AF:

0.400

Gnomad ASJ exome

AF:

0.620

Gnomad EAS exome

AF:

0.358

Gnomad SAS exome

AF:

0.470

Gnomad FIN exome

AF:

0.436

Gnomad NFE exome

AF:

0.575

Gnomad OTH exome

AF:

0.518

GnomAD4 exome

AF:

0.558

AC:

813391

AN:

1457970

Hom.:

231092

Cov.:

AF XY:

0.556

AC XY:

403340

AN XY:

725592

show subpopulations

Gnomad4 AFR exome

AF:

0.610

Gnomad4 AMR exome

AF:

0.408

Gnomad4 ASJ exome

AF:

0.622

Gnomad4 EAS exome

AF:

0.288

Gnomad4 SAS exome

AF:

0.476

Gnomad4 FIN exome

AF:

0.440

Gnomad4 NFE exome

AF:

0.583

Gnomad4 OTH exome

AF:

0.557

GnomAD4 genome

AF:

0.556

AC:

84415

AN:

151940

Hom.:

23906

Cov.:

AF XY:

0.547

AC XY:

40637

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.610

Gnomad4 AMR

AF:

0.489

Gnomad4 ASJ

AF:

0.624

Gnomad4 EAS

AF:

0.335

Gnomad4 SAS

AF:

0.492

Gnomad4 FIN

AF:

0.437

Gnomad4 NFE

AF:

0.575

Gnomad4 OTH

AF:

0.554

Alfa

AF:

0.573

Hom.:

43871

Bravo

AF:

0.561

Asia WGS

AF:

0.403

AC:

1403

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 15, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 71% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 66. Only high quality variants are reported. -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Developmental and epileptic encephalopathy, 11

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Seizures, benign familial infantile, 3;C3150987:Developmental and epileptic encephalopathy, 11

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Seizures, benign familial infantile, 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Episodic ataxia, type 9

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.5

DANN

Benign

0.66

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

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