rs2246127

Positions:

• chr13-46856344-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000621.5(HTR2A):​c.614-20705T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 152,012 control chromosomes in the GnomAD database, including 15,707 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 0.44 (15707 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HTR2A NM_000621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.147

Genes affected

HTR2A (HGNC:5293): (5-hydroxytryptamine receptor 2A) This gene encodes one of the receptors for serotonin, a neurotransmitter with many roles. Mutations in this gene are associated with susceptibility to schizophrenia and obsessive-compulsive disorder, and are also associated with response to the antidepressant citalopram in patients with major depressive disorder (MDD). MDD patients who also have a mutation in intron 2 of this gene show a significantly reduced response to citalopram as this antidepressant downregulates expression of this gene. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

HTR2A-AS1 (HGNC:40289): (HTR2A antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR2A	NM_000621.5	c.614-20705T>C		intron_variant		ENST00000542664.4
HTR2A-AS1	NR_046612.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR2A	ENST00000542664.4	c.614-20705T>C		intron_variant		1	NM_000621.5	P1
HTR2A	ENST00000543956.5	c.125-20705T>C		intron_variant		1
HTR2A-AS1	ENST00000455126.5			downstream_gene_variant		5
HTR2A-AS1	ENST00000430913.2			downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67522 AN: 151894 Hom.: 15694 Cov.: 32

Gnomad AFR AF: 0.565

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.415

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 FIN exome AF: 0.00

GnomAD4 genome AF: 0.445 AC: 67574 AN: 152012 Hom.: 15707 Cov.: 32 AF XY: 0.447 AC XY: 33216 AN XY: 74302

Gnomad4 AFR AF: 0.565

Gnomad4 AMR AF: 0.468

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.367

Gnomad4 SAS AF: 0.459

Gnomad4 FIN AF: 0.441

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.416

Alfa AF: 0.411 Hom.: 2751

Bravo AF: 0.450

Asia WGS AF: 0.437 AC: 1521 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	3.7
DANN	Benign	0.90

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

Other links and lift over

dbSNP: rs2246127; hg19: chr13-47430479;