rs2242446

Variant names:

• chr16-55656513-C-A
• rs2242446
• ENST00000379906.6:c.-182C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-55656513-C-A
• chr16-55656513-C-G
• chr16-55656513-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000379906.6(SLC6A2):​c.-182C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC6A2 ENST00000379906.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.247
• Publications: 100 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A2	NM_001172501.3	c.-51-131C>A		intron_variant	Intron 1 of 14	ENST00000568943.6	NP_001165972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A2	ENST00000568943.6	c.-51-131C>A		intron_variant	Intron 1 of 14	1	NM_001172501.3	ENSP00000457473.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 572014 Hom.: 0 Cov.: 7 AF XY: 0.00 AC XY: 0 AN XY: 301512

African (AFR) AF: 0.00 AC: 0 AN: 15198

American (AMR) AF: 0.00 AC: 0 AN: 25038

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15738

East Asian (EAS) AF: 0.00 AC: 0 AN: 33320

South Asian (SAS) AF: 0.00 AC: 0 AN: 53984

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32754

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2260

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 363492

Other (OTH) AF: 0.00 AC: 0 AN: 30230

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 164766

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	4.7
DANN	Benign	0.87
PhyloP100		-0.25
PromoterAI		-0.0012	Neutral

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

Other links and lift over

dbSNP: rs2242446; hg19: chr16-55690425;