6-55266339-A-G

Variant names:

• chr6-55266339-A-G
• rs2653342
• NM_001384272.1:c.762+2517A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001384272.1(HCRTR2):​c.762+2517A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.89 in 152,204 control chromosomes in the GnomAD database, including 60,617 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 0.89 (60617 hom., cov: 33)
• Consequence: HCRTR2 NM_001384272.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.961 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HCRTR2	NM_001384272.1	c.762+2517A>G		intron_variant	Intron 4 of 6	ENST00000370862.4	NP_001371201.1
HCRTR2	NM_001526.5	c.762+2517A>G		intron_variant	Intron 5 of 7		NP_001517.2
HCRTR2	XM_017010798.2	c.762+2517A>G		intron_variant	Intron 5 of 8		XP_016866287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HCRTR2	ENST00000370862.4	c.762+2517A>G		intron_variant	Intron 4 of 6	1	NM_001384272.1	ENSP00000359899.3
HCRTR2	ENST00000615358.4	c.762+2517A>G		intron_variant	Intron 5 of 7	1		ENSP00000477548.1

Frequencies

GnomAD3 genomes AF: 0.890 AC: 135365 AN: 152086 Hom.: 60559 Cov.: 33

Gnomad AFR AF: 0.969

Gnomad AMI AF: 0.935

Gnomad AMR AF: 0.900

Gnomad ASJ AF: 0.914

Gnomad EAS AF: 0.933

Gnomad SAS AF: 0.887

Gnomad FIN AF: 0.882

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.836

Gnomad OTH AF: 0.893

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

GnomAD4 genome AF: 0.890 AC: 135481 AN: 152204 Hom.: 60617 Cov.: 33 AF XY: 0.895 AC XY: 66544 AN XY: 74386

African (AFR) AF: 0.969 AC: 40260 AN: 41546

American (AMR) AF: 0.900 AC: 13745 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.914 AC: 3173 AN: 3472

East Asian (EAS) AF: 0.934 AC: 4833 AN: 5176

South Asian (SAS) AF: 0.887 AC: 4288 AN: 4834

European-Finnish (FIN) AF: 0.882 AC: 9346 AN: 10594

Middle Eastern (MID) AF: 0.925 AC: 272 AN: 294

European-Non Finnish (NFE) AF: 0.836 AC: 56829 AN: 67986

Other (OTH) AF: 0.889 AC: 1882 AN: 2116

Alfa AF: 0.854 Hom.: 28439

Bravo AF: 0.895

Asia WGS AF: 0.886 AC: 3080 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.010
DANN	Benign	0.32
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2653342; hg19: chr6-55131137;