rs2760351

chr13-46856180-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.614-20541T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 152,106 control chromosomes in the GnomAD database, including 35,215 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 0.67 (35215 hom., cov: 33)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: HTR2A NM_000621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR2A	NM_000621.5	c.614-20541T>C		intron_variant		ENST00000542664.4
HTR2A-AS1	NR_046612.1	n.322A>G		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR2A	ENST00000542664.4	c.614-20541T>C		intron_variant		1	NM_000621.5	P1
HTR2A	ENST00000543956.5	c.125-20541T>C		intron_variant		1
HTR2A-AS1	ENST00000455126.5	n.175A>G		non_coding_transcript_exon_variant	2/2	5
HTR2A-AS1	ENST00000430913.2	n.310A>G		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes AF: 0.674 AC: 102469 AN: 151986 Hom.: 35187 Cov.: 33

Gnomad AFR AF: 0.608

Gnomad AMI AF: 0.619

Gnomad AMR AF: 0.738

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.989

Gnomad SAS AF: 0.905

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.654

Gnomad OTH AF: 0.668

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.674 AC: 102537 AN: 152104 Hom.: 35215 Cov.: 33 AF XY: 0.684 AC XY: 50877 AN XY: 74350

Gnomad4 AFR AF: 0.608

Gnomad4 AMR AF: 0.739

Gnomad4 ASJ AF: 0.686

Gnomad4 EAS AF: 0.989

Gnomad4 SAS AF: 0.905

Gnomad4 FIN AF: 0.706

Gnomad4 NFE AF: 0.655

Gnomad4 OTH AF: 0.671

Alfa AF: 0.669 Hom.: 10030

Bravo AF: 0.672

Asia WGS AF: 0.914 AC: 3176 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.1
Dann	Benign	0.43

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: rs2760351; hg19: chr13-47430315;