Variant rs998424 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_001172501.3(SLC6A2):c.1389+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 1,613,250 control chromosomes in the GnomAD database, including 88,058 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 6229 hom., cov: 32)

Exomes 𝑓: 0.33 ( 81829 hom. )

Consequence

SLC6A2
NM_001172501.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.80

Variant links:

Genes affected

SLC6A2 (HGNC:11048): (solute carrier family 6 member 2) This gene encodes a member of the sodium:neurotransmitter symporter family. This member is a multi-pass membrane protein, which is responsible for reuptake of norepinephrine into presynaptic nerve terminals and is a regulator of norepinephrine homeostasis. Mutations in this gene cause orthostatic intolerance, a syndrome characterized by lightheadedness, fatigue, altered mentation and syncope. Alternatively spliced transcript variants encoding different isoforms have been identified in this gene.[provided by RefSeq, Feb 2010]

SLC6A2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 16-55698034-G-A is Benign according to our data. Variant chr16-55698034-G-A is described in ClinVar as [Benign]. Clinvar id is 1282997.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A2	NM_001172501.3 linkuse as main transcript	c.1389+9G>A		intron_variant		ENST00000568943.6	NP_001165972.1	P23975-1A0A024R6T9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A2	ENST00000568943.6 linkuse as main transcript	c.1389+9G>A		intron_variant		1	NM_001172501.3	ENSP00000457473.1		P23975-1

Frequencies

GnomAD3 genomes

AF:

0.266

AC:

40362

AN:

151954

Hom.:

6224

Cov.:

show subpopulations

Gnomad AFR

AF:

0.111

Gnomad AMI

AF:

0.375

Gnomad AMR

AF:

0.331

Gnomad ASJ

AF:

0.269

Gnomad EAS

AF:

0.277

Gnomad SAS

AF:

0.191

Gnomad FIN

AF:

0.353

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.334

Gnomad OTH

AF:

0.260

GnomAD3 exomes

AF:

0.312

AC:

78458

AN:

251348

Hom.:

13226

AF XY:

0.307

AC XY:

41748

AN XY:

135828

show subpopulations

Gnomad AFR exome

AF:

0.108

Gnomad AMR exome

AF:

0.414

Gnomad ASJ exome

AF:

0.275

Gnomad EAS exome

AF:

0.295

Gnomad SAS exome

AF:

0.198

Gnomad FIN exome

AF:

0.348

Gnomad NFE exome

AF:

0.341

Gnomad OTH exome

AF:

0.291

GnomAD4 exome

AF:

0.329

AC:

480022

AN:

1461176

Hom.:

81829

Cov.:

AF XY:

0.324

AC XY:

235852

AN XY:

726920

show subpopulations

Gnomad4 AFR exome

AF:

0.0968

Gnomad4 AMR exome

AF:

0.401

Gnomad4 ASJ exome

AF:

0.278

Gnomad4 EAS exome

AF:

0.265

Gnomad4 SAS exome

AF:

0.201

Gnomad4 FIN exome

AF:

0.344

Gnomad4 NFE exome

AF:

0.347

Gnomad4 OTH exome

AF:

0.301

GnomAD4 genome

AF:

0.265

AC:

40371

AN:

152074

Hom.:

6229

Cov.:

AF XY:

0.267

AC XY:

19839

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.111

Gnomad4 AMR

AF:

0.331

Gnomad4 ASJ

AF:

0.269

Gnomad4 EAS

AF:

0.276

Gnomad4 SAS

AF:

0.192

Gnomad4 FIN

AF:

0.353

Gnomad4 NFE

AF:

0.334

Gnomad4 OTH

AF:

0.257

Alfa

AF:

0.279

Hom.:

2835

Bravo

AF:

0.259

Asia WGS

AF:

0.206

AC:

718

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 28, 2020	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

6.7

DANN

Benign

0.76

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