rs2296972

Positions:

• chr13-46854336-A-C

Variant summary

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

The NM_000621.5(HTR2A):​c.614-18697T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.692 in 152,146 control chromosomes in the GnomAD database, including 36,831 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 0.69 (36828 hom., cov: 33)
  • Exomes 𝑓: 0.88 (3 hom.)
• Consequence: HTR2A NM_000621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.813

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR2A	NM_000621.5	c.614-18697T>G		intron_variant		ENST00000542664.4
HTR2A-AS1	NR_046612.1	n.231+254A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR2A	ENST00000542664.4	c.614-18697T>G		intron_variant		1	NM_000621.5	P1
HTR2A	ENST00000543956.5	c.125-18697T>G		intron_variant		1
HTR2A-AS1	ENST00000455126.5	n.85-1754A>C		intron_variant, non_coding_transcript_variant		5
HTR2A-AS1	ENST00000430913.2	n.219+254A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.692 AC: 105227 AN: 152020 Hom.: 36814 Cov.: 33

Gnomad AFR AF: 0.767

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.684

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.646

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.705

Gnomad OTH AF: 0.690

GnomAD4 exome AF: 0.875 AC: 7 AN: 8 Hom.: 3 AF XY: 0.833 AC XY: 5 AN XY: 6

Gnomad4 NFE exome AF: 0.833

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.692 AC: 105271 AN: 152138 Hom.: 36828 Cov.: 33 AF XY: 0.681 AC XY: 50645 AN XY: 74366

Gnomad4 AFR AF: 0.767

Gnomad4 AMR AF: 0.601

Gnomad4 ASJ AF: 0.684

Gnomad4 EAS AF: 0.471

Gnomad4 SAS AF: 0.511

Gnomad4 FIN AF: 0.646

Gnomad4 NFE AF: 0.705

Gnomad4 OTH AF: 0.685

Alfa AF: 0.691 Hom.: 20565

Bravo AF: 0.696

Asia WGS AF: 0.517 AC: 1796 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.34
DANN	Benign	0.69

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: rs2296972; hg19: chr13-47428471;