rs2296973

Positions:

• chr13-46892646-T-G

Variant summary

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

The NM_000621.5(HTR2A):​c.413-56A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 1,410,948 control chromosomes in the GnomAD database, including 354,615 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 0.73 (40460 hom., cov: 32)
  • Exomes 𝑓: 0.71 (314155 hom.)
• Consequence: HTR2A NM_000621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR2A	NM_000621.5	c.413-56A>C		intron_variant		ENST00000542664.4
HTR2A	NM_001165947.5	c.-77-56A>C		intron_variant
HTR2A	NM_001378924.1	c.413-56A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR2A	ENST00000542664.4	c.413-56A>C		intron_variant		1	NM_000621.5	P1
HTR2A	ENST00000543956.5	c.-77-56A>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110658 AN: 151988 Hom.: 40419 Cov.: 32

Gnomad AFR AF: 0.792

Gnomad AMI AF: 0.716

Gnomad AMR AF: 0.706

Gnomad ASJ AF: 0.765

Gnomad EAS AF: 0.660

Gnomad SAS AF: 0.657

Gnomad FIN AF: 0.669

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.711

Gnomad OTH AF: 0.736

GnomAD4 exome AF: 0.706 AC: 888148 AN: 1258842 Hom.: 314155 AF XY: 0.705 AC XY: 448810 AN XY: 636246

Gnomad4 AFR exome AF: 0.793

Gnomad4 AMR exome AF: 0.648

Gnomad4 ASJ exome AF: 0.765

Gnomad4 EAS exome AF: 0.624

Gnomad4 SAS exome AF: 0.663

Gnomad4 FIN exome AF: 0.661

Gnomad4 NFE exome AF: 0.713

Gnomad4 OTH exome AF: 0.712

GnomAD4 genome AF: 0.728 AC: 110755 AN: 152106 Hom.: 40460 Cov.: 32 AF XY: 0.724 AC XY: 53855 AN XY: 74352

Gnomad4 AFR AF: 0.792

Gnomad4 AMR AF: 0.706

Gnomad4 ASJ AF: 0.765

Gnomad4 EAS AF: 0.660

Gnomad4 SAS AF: 0.657

Gnomad4 FIN AF: 0.669

Gnomad4 NFE AF: 0.711

Gnomad4 OTH AF: 0.737

Alfa AF: 0.711 Hom.: 25514

Bravo AF: 0.731

Asia WGS AF: 0.682 AC: 2371 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.36

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: rs2296973; hg19: chr13-47466781; COSMIC: COSV66327343; COSMIC: COSV66327343;