13-46856128-C-G

Variant names:

• chr13-46856128-C-G
• rs2274639
• NM_000621.5:c.614-20489G>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000621.5(HTR2A):​c.614-20489G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,168 control chromosomes in the GnomAD database, including 2,384 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.16 (2384 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HTR2A NM_000621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.823

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-AS1 (HGNC:40289): (HTR2A antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR2A	NM_000621.5	c.614-20489G>C		intron_variant	Intron 3 of 3	ENST00000542664.4	NP_000612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR2A	ENST00000542664.4	c.614-20489G>C		intron_variant	Intron 3 of 3	1	NM_000621.5	ENSP00000437737.1
HTR2A	ENST00000543956.5	c.125-20489G>C		intron_variant	Intron 2 of 2	1		ENSP00000441861.2
HTR2A-AS1	ENST00000430913.2	n.258C>G		non_coding_transcript_exon_variant	Exon 3 of 3	3
HTR2A-AS1	ENST00000455126.5	n.123C>G		non_coding_transcript_exon_variant	Exon 2 of 2	5

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24068 AN: 152050 Hom.: 2373 Cov.: 32

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.0575

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.154

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.158 AC: 24117 AN: 152168 Hom.: 2384 Cov.: 32 AF XY: 0.157 AC XY: 11703 AN XY: 74404

Gnomad4 AFR AF: 0.277

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.0575

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.156

Alfa AF: 0.0358 Hom.: 27

Bravo AF: 0.171

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.42
DANN	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2274639; hg19: chr13-47430263;