rs6305

chr13-46892487-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000621.5(HTR2A):c.516C>T(p.Asp172=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0215 in 1,614,218 control chromosomes in the GnomAD database, including 446 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 0.017 (32 hom., cov: 33)
  • Exomes 𝑓: 0.022 (414 hom.)
• Consequence: HTR2A NM_000621.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP7: Synonymous conserved (PhyloP=1.12 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR2A	NM_000621.5	c.516C>T	p.Asp172=	synonymous_variant	3/4	ENST00000542664.4
HTR2A	NM_001378924.1	c.516C>T	p.Asp172=	synonymous_variant	3/4
HTR2A	NM_001165947.5	c.27C>T	p.Asp9=	synonymous_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR2A	ENST00000542664.4	c.516C>T	p.Asp172=	synonymous_variant	3/4	1	NM_000621.5	P1
HTR2A	ENST00000543956.5	c.27C>T	p.Asp9=	synonymous_variant	2/3	1

Frequencies

GnomAD3 genomes AF: 0.0173 AC: 2631 AN: 152226 Hom.: 33 Cov.: 33

Gnomad AFR AF: 0.00497

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0192

Gnomad ASJ AF: 0.0484

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00579

Gnomad FIN AF: 0.00339

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0268

Gnomad OTH AF: 0.0292

GnomAD3 exomes AF: 0.0183 AC: 4601 AN: 251492 Hom.: 57 AF XY: 0.0188 AC XY: 2560 AN XY: 135922

Gnomad AFR exome AF: 0.00418

Gnomad AMR exome AF: 0.0146

Gnomad ASJ exome AF: 0.0456

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00830

Gnomad FIN exome AF: 0.00383

Gnomad NFE exome AF: 0.0270

Gnomad OTH exome AF: 0.0261

GnomAD4 exome AF: 0.0220 AC: 32154 AN: 1461874 Hom.: 414 Cov.: 32 AF XY: 0.0222 AC XY: 16134 AN XY: 727242

Gnomad4 AFR exome AF: 0.00466

Gnomad4 AMR exome AF: 0.0152

Gnomad4 ASJ exome AF: 0.0447

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.00896

Gnomad4 FIN exome AF: 0.00545

Gnomad4 NFE exome AF: 0.0246

Gnomad4 OTH exome AF: 0.0230

GnomAD4 genome AF: 0.0172 AC: 2626 AN: 152344 Hom.: 32 Cov.: 33 AF XY: 0.0159 AC XY: 1183 AN XY: 74502

Gnomad4 AFR AF: 0.00498

Gnomad4 AMR AF: 0.0191

Gnomad4 ASJ AF: 0.0484

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00580

Gnomad4 FIN AF: 0.00339

Gnomad4 NFE AF: 0.0268

Gnomad4 OTH AF: 0.0289

Alfa AF: 0.0241 Hom.: 25

Bravo AF: 0.0177

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.0317

EpiControl AF: 0.0318

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
Cadd	Benign	9.0
Dann	Benign	0.73

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: rs6305; hg19: chr13-47466622;