13-46895721-T-G

Position:

• chr13-46895721-T-G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_000621.5(HTR2A):​c.186A>C​(p.Ser62=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HTR2A NM_000621.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.666

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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 13-46895721-T-G is Benign according to our data. Variant chr13-46895721-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 736153.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.666 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR2A	NM_000621.5	c.186A>C	p.Ser62=	synonymous_variant	2/4	ENST00000542664.4	NP_000612.1
HTR2A	NM_001378924.1	c.186A>C	p.Ser62=	synonymous_variant	2/4		NP_001365853.1
HTR2A	NM_001165947.5	c.-78+953A>C		intron_variant			NP_001159419.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR2A	ENST00000542664.4	c.186A>C	p.Ser62=	synonymous_variant	2/4	1	NM_000621.5	ENSP00000437737	P1
HTR2A	ENST00000543956.5	c.-78+953A>C		intron_variant		1		ENSP00000441861
HTR2A	ENST00000612998.1	c.93A>C	p.Ser31=	synonymous_variant	1/1			ENSP00000482708

Frequencies

GnomAD3 genomes AF: 0.00 AC: 36 AN: 151892 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000328

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000774

Gnomad SAS AF: 0.00125

Gnomad FIN AF: 0.0000946

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00118 AC: 1708 AN: 1452048 Hom.: 0 Cov.: 31 AF XY: 0.00112 AC XY: 806 AN XY: 722632

Gnomad4 AFR exome AF: 0.000931

Gnomad4 AMR exome AF: 0.0000448

Gnomad4 ASJ exome AF: 0.000768

Gnomad4 EAS exome AF: 0.000177

Gnomad4 SAS exome AF: 0.000453

Gnomad4 FIN exome AF: 0.000188

Gnomad4 NFE exome AF: 0.00140

Gnomad4 OTH exome AF: 0.000900

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000237 AC: 36 AN: 152010 Hom.: 0 Cov.: 32 AF XY: 0.000283 AC XY: 21 AN XY: 74298

Gnomad4 AFR AF: 0.000145

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000776

Gnomad4 SAS AF: 0.00125

Gnomad4 FIN AF: 0.0000946

Gnomad4 NFE AF: 0.000221

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000282 Hom.: 0

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.7
DANN	Benign	0.61

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: rs1190153612; hg19: chr13-47469856;