dbSNP rs15534: SLC6A2:c.*269C>T (chr16-55702615-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001172501.3(SLC6A2):c.*269C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 1,389,152 control chromosomes in the GnomAD database, including 21,543 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.21 ( 3749 hom., cov: 32)

Exomes 𝑓: 0.16 ( 17794 hom. )

Consequence

SLC6A2
NM_001172501.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.597

Publications

11 publications found

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 Gene-Disease associations (from GenCC):

postural orthostatic tachycardia syndrome
Inheritance: Unknown, AD Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

SLC6A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A2	NM_001172501.3 link	c.*269C>T		3_prime_UTR_variant	Exon 15 of 15	ENST00000568943.6	NP_001165972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A2	ENST00000568943.6 link	c.*269C>T		3_prime_UTR_variant	Exon 15 of 15	1	NM_001172501.3	ENSP00000457473.1

Frequencies

GnomAD3 genomes

AF:

0.206

AC:

31223

AN:

151832

Hom.:

3737

Cov.:

show subpopulations

Gnomad AFR

AF:

0.335

Gnomad AMI

AF:

0.233

Gnomad AMR

AF:

0.130

Gnomad ASJ

AF:

0.157

Gnomad EAS

AF:

0.0340

Gnomad SAS

AF:

0.200

Gnomad FIN

AF:

0.192

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.162

Gnomad OTH

AF:

0.201

GnomAD4 exome

AF:

0.164

AC:

203244

AN:

1237202

Hom.:

17794

Cov.:

AF XY:

0.165

AC XY:

98697

AN XY:

597710

show subpopulations

African (AFR)

AF:

0.346

AC:

9394

AN:

27174

American (AMR)

AF:

0.106

AC:

1980

AN:

18652

Ashkenazi Jewish (ASJ)

AF:

0.148

AC:

2574

AN:

17414

East Asian (EAS)

AF:

0.0305

AC:

940

AN:

30830

South Asian (SAS)

AF:

0.194

AC:

11721

AN:

60350

European-Finnish (FIN)

AF:

0.178

AC:

4632

AN:

25974

Middle Eastern (MID)

AF:

0.200

AC:

679

AN:

3396

European-Non Finnish (NFE)

AF:

0.162

AC:

162616

AN:

1002886

Other (OTH)

AF:

0.172

AC:

8708

AN:

50526

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

8246

16492

24738

32984

41230

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6288

12576

18864

25152

31440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.206

AC:

31280

AN:

151950

Hom.:

3749

Cov.:

AF XY:

0.205

AC XY:

15230

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.335

AC:

13871

AN:

41406

American (AMR)

AF:

0.130

AC:

1983

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.157

AC:

544

AN:

3470

East Asian (EAS)

AF:

0.0340

AC:

176

AN:

5172

South Asian (SAS)

AF:

0.201

AC:

966

AN:

4808

European-Finnish (FIN)

AF:

0.192

AC:

2021

AN:

10552

Middle Eastern (MID)

AF:

0.197

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.162

AC:

11028

AN:

67950

Other (OTH)

AF:

0.199

AC:

421

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1183

2366

3550

4733

5916

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

328

656

984

1312

1640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.173

Hom.:

3086

Bravo

AF:

0.206

Asia WGS

AF:

0.134

AC:

468

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.1

(source)

DANN

Benign

0.51

PhyloP100

-0.60

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over