rs6313

chr13-46895805-G-Achr13-46895805-G-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.35

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 -15 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_single_submitter, 1 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	UniProt
HTR2A	NM_000621.5	c.102C>T	p.Ser34=	synonymous_variant	2/4	ENST00000542664.4
HTR2A	NM_001378924.1	c.102C>T	p.Ser34=	synonymous_variant	2/4
HTR2A	NM_001165947.5	c.-78+869C>T		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61037 AN: 151936 Hom.: 12506 Cov.: 32

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

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.: 40 AF XY: 0.410 AC XY: 298131 AN XY: 727156

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.: 32 AF XY: 0.401 AC XY: 29794 AN XY: 74328

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:1

Revision: criteria provided, single submitter

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. -

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

Other links and lift over

dbSNP: rs6313; hg19: chr13-47469940; COSMIC: COSV66327259;