2-208643567-C-T

Position:

• chr2-208643567-C-T

Variant summary

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

The NR_136588.1(LOC101927960):​n.506-13259C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0449 in 152,170 control chromosomes in the GnomAD database, including 312 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 0.045 (312 hom., cov: 32)
• Consequence: LOC101927960 NR_136588.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.295

Genes affected

LOC101927960 (HGNC:):

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]

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 (AFR) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC101927960	NR_136588.1	n.506-13259C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTH2R	ENST00000419079.1	c.*99-13259C>T		intron_variant, NMD_transcript_variant		2		ENSP00000393930

Frequencies

GnomAD3 genomes AF: 0.0449 AC: 6829 AN: 152052 Hom.: 314 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0221

Gnomad ASJ AF: 0.00950

Gnomad EAS AF: 0.0270

Gnomad SAS AF: 0.0655

Gnomad FIN AF: 0.00518

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0147

Gnomad OTH AF: 0.0374

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

GnomAD4 genome AF: 0.0449 AC: 6835 AN: 152170 Hom.: 312 Cov.: 32 AF XY: 0.0441 AC XY: 3283 AN XY: 74396

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.0221

Gnomad4 ASJ AF: 0.00950

Gnomad4 EAS AF: 0.0269

Gnomad4 SAS AF: 0.0650

Gnomad4 FIN AF: 0.00518

Gnomad4 NFE AF: 0.0147

Gnomad4 OTH AF: 0.0365

Alfa AF: 0.0198 Hom.: 71

Bravo AF: 0.0488

Asia WGS AF: 0.0540 AC: 189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.36

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10497908; hg19: chr2-209508291;