rs2428707

Variant names:

• chrX-114765807-T-C
• rs2428707
• NM_000868.4:c.349+34200T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000868.4(HTR2C):​c.349+34200T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.76 (23507 hom., 24894 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: HTR2C NM_000868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0160
• Publications: 8 publications found

Genes affected

HTR2C (HGNC:5295): (5-hydroxytryptamine receptor 2C) This gene encodes a seven-transmembrane G-protein-coupled receptor. The encoded protein responds to signaling through the neurotransmitter serotonin. The mRNA of this gene is subject to multiple RNA editing events, where adenosine residues encoded by the genome are converted to inosines. RNA editing is predicted to alter the structure of the second intracellular loop, thereby generating alternate protein forms with decreased ability to interact with G proteins. Abnormalities in RNA editing of this gene have been detected in victims of suicide that suffer from depression. In addition, naturally-occuring variation in the promoter and 5' non-coding and coding regions of this gene may show statistically-significant association with mental illness and behavioral disorders. Alternative splicing results in multiple different transcript variants. [provided by RefSeq, Jan 2015]

ENSG00000306059 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR2C	NM_000868.4	c.349+34200T>C		intron_variant	Intron 4 of 5	ENST00000276198.6	NP_000859.2
HTR2C	NM_001256760.3	c.349+34200T>C		intron_variant	Intron 5 of 6		NP_001243689.2
HTR2C	NM_001256761.3	c.349+34200T>C		intron_variant	Intron 4 of 5		NP_001243690.2
LOC105373313	XR_001755943.2	n.573+23536A>G		intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR2C	ENST00000276198.6	c.349+34200T>C		intron_variant	Intron 4 of 5	1	NM_000868.4	ENSP00000276198.1

Frequencies

GnomAD3 genomes AF: 0.765 AC: 84140 AN: 109943 Hom.: 23519 Cov.: 22

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.811

Gnomad AMR AF: 0.885

Gnomad ASJ AF: 0.814

Gnomad EAS AF: 0.990

Gnomad SAS AF: 0.892

Gnomad FIN AF: 0.882

Gnomad MID AF: 0.815

Gnomad NFE AF: 0.844

Gnomad OTH AF: 0.821

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.765 AC: 84136 AN: 109990 Hom.: 23507 Cov.: 22 AF XY: 0.771 AC XY: 24894 AN XY: 32268

African (AFR) AF: 0.521 AC: 15783 AN: 30316

American (AMR) AF: 0.885 AC: 9011 AN: 10184

Ashkenazi Jewish (ASJ) AF: 0.814 AC: 2139 AN: 2628

East Asian (EAS) AF: 0.990 AC: 3489 AN: 3525

South Asian (SAS) AF: 0.892 AC: 2270 AN: 2546

European-Finnish (FIN) AF: 0.882 AC: 5031 AN: 5706

Middle Eastern (MID) AF: 0.791 AC: 167 AN: 211

European-Non Finnish (NFE) AF: 0.844 AC: 44462 AN: 52693

Other (OTH) AF: 0.821 AC: 1236 AN: 1505

Alfa AF: 0.809 Hom.: 11978

Bravo AF: 0.756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.5
PhyloP100		-0.016

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2428707; hg19: chrX-114000359;