NM_001309516.2:c.-258-23516C>G

Variant names:

• chr2-208404685-C-G
• rs9288393
• NM_001309516.2:c.-258-23516C>G

Variant summary

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

The NM_001309516.2(PTH2R):​c.-258-23516C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,050 control chromosomes in the GnomAD database, including 3,178 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 0.20 (3178 hom., cov: 32)
• Consequence: PTH2R NM_001309516.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.872
• Publications: 2 publications found

Genes affected

PTH2R (HGNC:9609): (parathyroid hormone 2 receptor) The protein encoded by this gene is a member of the G-protein coupled receptor 2 family. This protein is a receptor for parathyroid hormone (PTH). This receptor is more selective in ligand recognition and has a more specific tissue distribution compared to parathyroid hormone receptor 1 (PTHR1). It is activated only by PTH and not by parathyroid hormone-like hormone (PTHLH) and is particularly abundant in brain and pancreas. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]

LOC105373855 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTH2R	NM_001309516.2	c.-258-23516C>G		intron_variant	Intron 1 of 12		NP_001296445.1
PTH2R	NM_001371905.1	c.-325-10835C>G		intron_variant	Intron 1 of 13		NP_001358834.1
PTH2R	NM_001371906.1	c.-334-12176C>G		intron_variant	Intron 1 of 13		NP_001358835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTH2R	ENST00000617735.4	c.-258-23516C>G		intron_variant	Intron 1 of 12	2		ENSP00000482485.1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29757 AN: 151932 Hom.: 3179 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.0656

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.196 AC: 29769 AN: 152050 Hom.: 3178 Cov.: 32 AF XY: 0.194 AC XY: 14436 AN XY: 74308

African (AFR) AF: 0.122 AC: 5071 AN: 41488

American (AMR) AF: 0.203 AC: 3096 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 903 AN: 3468

East Asian (EAS) AF: 0.0658 AC: 340 AN: 5170

South Asian (SAS) AF: 0.262 AC: 1261 AN: 4808

European-Finnish (FIN) AF: 0.202 AC: 2132 AN: 10568

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.241 AC: 16350 AN: 67974

Other (OTH) AF: 0.182 AC: 383 AN: 2106

Alfa AF: 0.125 Hom.: 200

Bravo AF: 0.190

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.0
DANN	Benign	0.66
PhyloP100		0.87

Splicing

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

Other links and lift over

dbSNP: rs9288393; hg19: chr2-209269410;