NM_000621.5:c.102C>T

Variant names:

• chr13-46895805-G-A
• rs6313
• NM_000621.5:c.102C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000621.5(HTR2A):​c.102C>T​(p.Ser34Ser) 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.35
• Publications: 789 publications found

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]

ENSG00000301465 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
HTR2A	NM_000621.5	c.102C>T	p.Ser34Ser	synonymous_variant	Exon 2 of 4	ENST00000542664.4	NP_000612.1
HTR2A	NM_001378924.1	c.102C>T	p.Ser34Ser	synonymous_variant	Exon 2 of 4		NP_001365853.1
HTR2A	NM_001165947.5	c.-78+869C>T		intron_variant	Intron 1 of 2		NP_001159419.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR2A	ENST00000542664.4	c.102C>T	p.Ser34Ser	synonymous_variant	Exon 2 of 4	1	NM_000621.5	ENSP00000437737.1

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

GnomAD2 exomes AF: 0.408 AC: 102506 AN: 251386 AF XY: 0.413

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 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

African (AFR) AF: 0.378 AC: 12656 AN: 33478

American (AMR) AF: 0.336 AC: 15034 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 13095 AN: 26134

East Asian (EAS) AF: 0.541 AC: 21487 AN: 39700

South Asian (SAS) AF: 0.420 AC: 36189 AN: 86254

European-Finnish (FIN) AF: 0.323 AC: 17254 AN: 53382

Middle Eastern (MID) AF: 0.523 AC: 3015 AN: 5768

European-Non Finnish (NFE) AF: 0.406 AC: 451434 AN: 1111878

Other (OTH) AF: 0.427 AC: 25795 AN: 60378

GnomAD4 genome AF: 0.402 AC: 61059 AN: 152054 Hom.: 12507 Cov.: 32 AF XY: 0.401 AC XY: 29794 AN XY: 74328

African (AFR) AF: 0.377 AC: 15638 AN: 41460

American (AMR) AF: 0.390 AC: 5954 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1724 AN: 3466

East Asian (EAS) AF: 0.585 AC: 3037 AN: 5188

South Asian (SAS) AF: 0.415 AC: 1999 AN: 4818

European-Finnish (FIN) AF: 0.336 AC: 3550 AN: 10576

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.410 AC: 27855 AN: 67960

Other (OTH) AF: 0.447 AC: 946 AN: 2114

Alfa AF: 0.413 Hom.: 65009

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

Submissions by phenotype

not specified Benign:1

Mar 09, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	5.9
DANN	Benign	0.60
PhyloP100		-1.3
PromoterAI		-0.0013	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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