Variant 13-46835596-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_000621.5(HTR2A):c.657G>A(p.Ser219=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00126 in 1,613,904 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00093 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 0 hom. )

Consequence

HTR2A
NM_000621.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.00

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 13-46835596-C-T is Benign according to our data. Variant chr13-46835596-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 712185.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-46835596-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=2 with no splicing effect.

BS2

High AC in GnomAd4 at 142 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
HTR2A	NM_000621.5 linkuse as main transcript	c.657G>A	p.Ser219=	synonymous_variant	4/4	ENST00000542664.4	NP_000612.1
HTR2A	NM_001378924.1 linkuse as main transcript	c.657G>A	p.Ser219=	synonymous_variant	4/4		NP_001365853.1
HTR2A	NM_001165947.5 linkuse as main transcript	c.168G>A	p.Ser56=	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.657G>A	p.Ser219=	synonymous_variant	4/4	1	NM_000621.5	ENSP00000437737	P1	P28223-1
HTR2A	ENST00000543956.5 linkuse as main transcript	c.168G>A	p.Ser56=	synonymous_variant	3/3	1		ENSP00000441861

Frequencies

GnomAD3 genomes

AF:

0.000933

AC:

142

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000434

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00293

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00129

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00106

AC:

265

AN:

250820

Hom.:

AF XY:

0.000996

AC XY:

135

AN XY:

135570

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.0000869

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00259

Gnomad NFE exome

AF:

0.00166

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00129

AC:

1889

AN:

1461662

Hom.:

Cov.:

AF XY:

0.00125

AC XY:

906

AN XY:

727128

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.00268

Gnomad4 NFE exome

AF:

0.00148

Gnomad4 OTH exome

AF:

0.00103

GnomAD4 genome

AF:

0.000933

AC:

142

AN:

152242

Hom.:

Cov.:

AF XY:

0.000846

AC XY:

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00293

Gnomad4 NFE

AF:

0.00129

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00110

Hom.:

Bravo

AF:

0.000706

EpiCase

AF:

0.00120

EpiControl

AF:

0.000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 21, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

6.3

DANN

Benign

0.66

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over