Variant rs6305 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.12

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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	Protein
HTR2A	NM_000621.5 linkuse as main transcript	c.516C>T	p.Asp172=	synonymous_variant	3/4	ENST00000542664.4	NP_000612.1
HTR2A	NM_001378924.1 linkuse as main transcript	c.516C>T	p.Asp172=	synonymous_variant	3/4		NP_001365853.1
HTR2A	NM_001165947.5 linkuse as main transcript	c.27C>T	p.Asp9=	synonymous_variant	2/3		NP_001159419.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR2A	ENST00000542664.4 linkuse as main transcript	c.516C>T	p.Asp172=	synonymous_variant	3/4	1	NM_000621.5	ENSP00000437737	P1	P28223-1
HTR2A	ENST00000543956.5 linkuse as main transcript	c.27C>T	p.Asp9=	synonymous_variant	2/3	1		ENSP00000441861

Frequencies

GnomAD3 genomes

AF:

0.0173

AC:

2631

AN:

152226

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.0188

AC XY:

2560

AN XY:

135922

show subpopulations

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.:

AF XY:

0.0222

AC XY:

16134

AN XY:

727242

show subpopulations

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.:

Cov.:

AF XY:

0.0159

AC XY:

1183

AN XY:

74502

show subpopulations

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.:

Bravo

AF:

0.0177

Asia WGS

AF:

0.00346

AC:

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over