Variant chr13-46895805-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000621.5(HTR2A):c.102C>T(p.Ser34=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 1,613,746 control chromosomes in the GnomAD database, including 135,757 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 12507 hom., cov: 32)

Exomes 𝑓: 0.41 ( 123250 hom. )

Consequence

HTR2A
NM_000621.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.35

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 13-46895805-G-A is Benign according to our data. Variant chr13-46895805-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 511089.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.35 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.568 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.102C>T	p.Ser34=	synonymous_variant	2/4	ENST00000542664.4	NP_000612.1
HTR2A	NM_001378924.1 linkuse as main transcript	c.102C>T	p.Ser34=	synonymous_variant	2/4		NP_001365853.1
HTR2A	NM_001165947.5 linkuse as main transcript	c.-78+869C>T		intron_variant			NP_001159419.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR2A	ENST00000542664.4 linkuse as main transcript	c.102C>T	p.Ser34=	synonymous_variant	2/4	1	NM_000621.5	ENSP00000437737	P1	P28223-1
HTR2A	ENST00000543956.5 linkuse as main transcript	c.-78+869C>T		intron_variant		1		ENSP00000441861
HTR2A	ENST00000612998.1 linkuse as main transcript	c.9C>T	p.Ser3=	synonymous_variant	1/1			ENSP00000482708

Frequencies

GnomAD3 genomes

AF:

0.402

AC:

61037

AN:

151936

Hom.:

12506

Cov.:

show subpopulations

Gnomad AFR

AF:

0.378

Gnomad AMI

AF:

0.221

Gnomad AMR

AF:

0.390

Gnomad ASJ

AF:

0.497

Gnomad EAS

AF:

0.585

Gnomad SAS

AF:

0.415

Gnomad FIN

AF:

0.336

Gnomad MID

AF:

0.532

Gnomad NFE

AF:

0.410

Gnomad OTH

AF:

0.447

GnomAD3 exomes

AF:

0.408

AC:

102506

AN:

251386

Hom.:

21805

AF XY:

0.413

AC XY:

56076

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.376

Gnomad AMR exome

AF:

0.330

Gnomad ASJ exome

AF:

0.500

Gnomad EAS exome

AF:

0.593

Gnomad SAS exome

AF:

0.414

Gnomad FIN exome

AF:

0.327

Gnomad NFE exome

AF:

0.411

Gnomad OTH exome

AF:

0.413

GnomAD4 exome

AF:

0.408

AC:

595959

AN:

1461692

Hom.:

123250

Cov.:

AF XY:

0.410

AC XY:

298131

AN XY:

727156

show subpopulations

Gnomad4 AFR exome

AF:

0.378

Gnomad4 AMR exome

AF:

0.336

Gnomad4 ASJ exome

AF:

0.501

Gnomad4 EAS exome

AF:

0.541

Gnomad4 SAS exome

AF:

0.420

Gnomad4 FIN exome

AF:

0.323

Gnomad4 NFE exome

AF:

0.406

Gnomad4 OTH exome

AF:

0.427

GnomAD4 genome

AF:

0.402

AC:

61059

AN:

152054

Hom.:

12507

Cov.:

AF XY:

0.401

AC XY:

29794

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.377

Gnomad4 AMR

AF:

0.390

Gnomad4 ASJ

AF:

0.497

Gnomad4 EAS

AF:

0.585

Gnomad4 SAS

AF:

0.415

Gnomad4 FIN

AF:

0.336

Gnomad4 NFE

AF:

0.410

Gnomad4 OTH

AF:

0.447

Alfa

AF:

0.419

Hom.:

32640

Bravo

AF:

0.403

Asia WGS

AF:

0.490

AC:

1705

AN:

3478

EpiCase

AF:

0.429

EpiControl

AF:

0.445

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 09, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

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

-0.72

CADD

Benign

5.9

DANN

Benign

0.60

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