rs2192372

chrX-114657295-A-GchrX-114657295-A-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000868.4(HTR2C):c.-80+43414A>G 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 0.66 (16837 hom., 20887 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: HTR2C NM_000868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BS2: High Homozygotes in GnomAd at 16847 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR2C	NM_000868.4	c.-80+43414A>G		intron_variant		ENST00000276198.6
HTR2C	NM_001256760.3	c.-171+43414A>G		intron_variant
HTR2C	NM_001256761.3	c.-80+43414A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR2C	ENST00000276198.6	c.-80+43414A>G		intron_variant		1	NM_000868.4	P1
HTR2C	ENST00000371950.3	c.-80+43414A>G		intron_variant		1
HTR2C	ENST00000371951.5	c.-171+43414A>G		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.655 AC: 71668 AN: 109371 Hom.: 16847 Cov.: 22 AF XY: 0.655 AC XY: 20860 AN XY: 31865

Gnomad AFR AF: 0.580

Gnomad AMI AF: 0.791

Gnomad AMR AF: 0.742

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.733

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.702

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: 0.655 AC: 71683 AN: 109420 Hom.: 16837 Cov.: 22 AF XY: 0.654 AC XY: 20887 AN XY: 31924

Gnomad4 AFR AF: 0.580

Gnomad4 AMR AF: 0.742

Gnomad4 ASJ AF: 0.637

Gnomad4 EAS AF: 0.851

Gnomad4 SAS AF: 0.557

Gnomad4 FIN AF: 0.733

Gnomad4 NFE AF: 0.663

Gnomad4 OTH AF: 0.702

Alfa AF: 0.658 Hom.: 4942

Bravo AF: 0.660

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	2.2

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2192372; hg19: chrX-113891773;