Variant 2-208437603-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_005048.4(PTH2R):c.245C>A(p.Ser82Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0178 in 1,613,320 control chromosomes in the GnomAD database, including 316 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.012 ( 18 hom., cov: 32)

Exomes 𝑓: 0.018 ( 298 hom. )

Consequence

PTH2R
NM_005048.4 stop_gained

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.0960

Variant links:

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]

PTH2R links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 2-208437603-C-A is Benign according to our data. Variant chr2-208437603-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3056501.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0121 (1845/152146) while in subpopulation NFE AF= 0.021 (1425/67992). AF 95% confidence interval is 0.0201. There are 18 homozygotes in gnomad4. There are 805 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTH2R	NM_005048.4 linkuse as main transcript	c.245C>A	p.Ser82Ter	stop_gained	3/13	ENST00000272847.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTH2R	ENST00000272847.7 linkuse as main transcript	c.245C>A	p.Ser82Ter	stop_gained	3/13	1	NM_005048.4	P1
PTH2R	ENST00000617735.4 linkuse as main transcript	c.-89C>A		5_prime_UTR_variant	3/13	2

Frequencies

GnomAD3 genomes

AF:

0.0121

AC:

1844

AN:

152030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00382

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0113

Gnomad ASJ

AF:

0.00692

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00265

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0210

Gnomad OTH

AF:

0.0144

GnomAD3 exomes

AF:

0.0119

AC:

2981

AN:

250978

Hom.:

AF XY:

0.0120

AC XY:

1633

AN XY:

135738

show subpopulations

Gnomad AFR exome

AF:

0.00317

Gnomad AMR exome

AF:

0.00860

Gnomad ASJ exome

AF:

0.00873

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00173

Gnomad FIN exome

AF:

0.00324

Gnomad NFE exome

AF:

0.0207

Gnomad OTH exome

AF:

0.0113

GnomAD4 exome

AF:

0.0183

AC:

26806

AN:

1461174

Hom.:

298

Cov.:

AF XY:

0.0177

AC XY:

12869

AN XY:

726836

show subpopulations

Gnomad4 AFR exome

AF:

0.00320

Gnomad4 AMR exome

AF:

0.00828

Gnomad4 ASJ exome

AF:

0.00785

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00211

Gnomad4 FIN exome

AF:

0.00380

Gnomad4 NFE exome

AF:

0.0223

Gnomad4 OTH exome

AF:

0.0148

GnomAD4 genome

AF:

0.0121

AC:

1845

AN:

152146

Hom.:

Cov.:

AF XY:

0.0108

AC XY:

805

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.00381

Gnomad4 AMR

AF:

0.0113

Gnomad4 ASJ

AF:

0.00692

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00125

Gnomad4 FIN

AF:

0.00265

Gnomad4 NFE

AF:

0.0210

Gnomad4 OTH

AF:

0.0143

Alfa

AF:

0.0174

Hom.:

Bravo

AF:

0.0129

TwinsUK

AF:

0.0218

AC:

ALSPAC

AF:

0.0202

AC:

ExAC

AF:

0.0126

AC:

1525

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0171

EpiControl

AF:

0.0188

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PTH2R-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 09, 2021

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Uncertain

0.0

CADD

Pathogenic

DANN

Benign

0.95

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.11

MutationTaster

Benign

1.0

Vest4

0.82

GERP RS

-3.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.23

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.23

Position offset: 44

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over