Variant chr2-208407049-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_005048.4(PTH2R):c.6C>A(p.Ala2=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00415 in 1,392,932 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0032 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0043 ( 13 hom. )

Consequence

PTH2R
NM_005048.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.203

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 2-208407049-C-A is Benign according to our data. Variant chr2-208407049-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 779079.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.203 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTH2R	NM_005048.4 linkuse as main transcript	c.6C>A	p.Ala2=	synonymous_variant	1/13	ENST00000272847.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTH2R	ENST00000272847.7 linkuse as main transcript	c.6C>A	p.Ala2=	synonymous_variant	1/13	1	NM_005048.4	P1
PTH2R	ENST00000617735.4 linkuse as main transcript	c.-258-21152C>A		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00319

AC:

486

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.000982

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00455

Gnomad FIN

AF:

0.00320

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00526

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00402

AC:

521

AN:

129672

Hom.:

AF XY:

0.00402

AC XY:

282

AN XY:

70194

show subpopulations

Gnomad AFR exome

AF:

0.000908

Gnomad AMR exome

AF:

0.00112

Gnomad ASJ exome

AF:

0.00624

Gnomad EAS exome

AF:

0.000124

Gnomad SAS exome

AF:

0.00437

Gnomad FIN exome

AF:

0.00523

Gnomad NFE exome

AF:

0.00490

Gnomad OTH exome

AF:

0.00512

GnomAD4 exome

AF:

0.00426

AC:

5289

AN:

1240674

Hom.:

Cov.:

AF XY:

0.00438

AC XY:

2650

AN XY:

604728

show subpopulations

Gnomad4 AFR exome

AF:

0.000588

Gnomad4 AMR exome

AF:

0.00120

Gnomad4 ASJ exome

AF:

0.00387

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00501

Gnomad4 FIN exome

AF:

0.00590

Gnomad4 NFE exome

AF:

0.00453

Gnomad4 OTH exome

AF:

0.00286

GnomAD4 genome

AF:

0.00319

AC:

486

AN:

152258

Hom.:

Cov.:

AF XY:

0.00290

AC XY:

216

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.000794

Gnomad4 AMR

AF:

0.000980

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00455

Gnomad4 FIN

AF:

0.00320

Gnomad4 NFE

AF:

0.00526

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00550

Hom.:

Bravo

AF:

0.00276

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2022	PTH2R: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

8.6

DANN

Benign

0.80

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

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