Variant 13-46835566-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_000621.5(HTR2A):c.687C>T(p.Leu229=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00187 in 1,614,012 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 6 hom. )

Consequence

HTR2A
NM_000621.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.71

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 13-46835566-G-A is Benign according to our data. Variant chr13-46835566-G-A is described in ClinVar as [Benign]. Clinvar id is 723564.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr13-46835566-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-3.71 with no splicing effect.

BS2

High AC in GnomAd4 at 182 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
HTR2A	NM_000621.5 linkuse as main transcript	c.687C>T	p.Leu229=	synonymous_variant	4/4	ENST00000542664.4	NP_000612.1
HTR2A	NM_001378924.1 linkuse as main transcript	c.687C>T	p.Leu229=	synonymous_variant	4/4		NP_001365853.1
HTR2A	NM_001165947.5 linkuse as main transcript	c.198C>T	p.Leu66=	synonymous_variant	3/3		NP_001159419.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR2A	ENST00000542664.4 linkuse as main transcript	c.687C>T	p.Leu229=	synonymous_variant	4/4	1	NM_000621.5	ENSP00000437737	P1	P28223-1
HTR2A	ENST00000543956.5 linkuse as main transcript	c.198C>T	p.Leu66=	synonymous_variant	3/3	1		ENSP00000441861

Frequencies

GnomAD3 genomes

AF:

0.00120

AC:

182

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00213

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00134

AC:

337

AN:

250954

Hom.:

AF XY:

0.00138

AC XY:

187

AN XY:

135614

show subpopulations

Gnomad AFR exome

AF:

0.000616

Gnomad AMR exome

AF:

0.0000869

Gnomad ASJ exome

AF:

0.000596

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00116

Gnomad NFE exome

AF:

0.00253

Gnomad OTH exome

AF:

0.000816

GnomAD4 exome

AF:

0.00194

AC:

2836

AN:

1461736

Hom.:

Cov.:

AF XY:

0.00189

AC XY:

1376

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.000459

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00191

Gnomad4 NFE exome

AF:

0.00237

Gnomad4 OTH exome

AF:

0.00129

GnomAD4 genome

AF:

0.00120

AC:

182

AN:

152276

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000481

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00213

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00204

Hom.:

Bravo

AF:

0.00120

EpiCase

AF:

0.00125

EpiControl

AF:

0.00207

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 21, 2018

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.13

DANN

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over