rs2134294

Positions:

• chr6-55269449-T-C
• chr6-55269449-T-G

Variant summary

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

The NM_001384272.1(HCRTR2):​c.762+5627T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 151,972 control chromosomes in the GnomAD database, including 17,348 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 0.47 (17348 hom., cov: 32)
• Consequence: HCRTR2 NM_001384272.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.479

Genes affected

HCRTR2 (HGNC:4849): (hypocretin receptor 2) The protein encoded by this gene is a G-protein coupled receptor involved in the regulation of feeding behavior. The encoded protein binds the hypothalamic neuropeptides orexin A and orexin B. A related gene (HCRTR1) encodes a G-protein coupled receptor that selectively binds orexin A. [provided by RefSeq, Jan 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HCRTR2	NM_001384272.1	c.762+5627T>C		intron_variant		ENST00000370862.4	NP_001371201.1
HCRTR2	NM_001526.5	c.762+5627T>C		intron_variant			NP_001517.2
HCRTR2	XM_017010798.2	c.762+5627T>C		intron_variant			XP_016866287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HCRTR2	ENST00000370862.4	c.762+5627T>C		intron_variant		1	NM_001384272.1	ENSP00000359899	P1
HCRTR2	ENST00000615358.4	c.762+5627T>C		intron_variant		1		ENSP00000477548	P1

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71100 AN: 151856 Hom.: 17347 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.593

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.579

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.478

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

GnomAD4 genome AF: 0.468 AC: 71115 AN: 151972 Hom.: 17348 Cov.: 32 AF XY: 0.473 AC XY: 35175 AN XY: 74294

Gnomad4 AFR AF: 0.343

Gnomad4 AMR AF: 0.443

Gnomad4 ASJ AF: 0.593

Gnomad4 EAS AF: 0.354

Gnomad4 SAS AF: 0.581

Gnomad4 FIN AF: 0.581

Gnomad4 NFE AF: 0.522

Gnomad4 OTH AF: 0.477

Alfa AF: 0.510 Hom.: 23239

Bravo AF: 0.448

Asia WGS AF: 0.472 AC: 1633 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.3
DANN	Benign	0.78

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: rs2134294; hg19: chr6-55134247;