6-52053170-T-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_138694.4(PKHD1):c.2046A>C(p.Pro682Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0974 in 1,614,084 control chromosomes in the GnomAD database, including 8,321 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.078 ( 574 hom., cov: 32)

Exomes 𝑓: 0.099 ( 7747 hom. )

Consequence

PKHD1
NM_138694.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -5.03

Variant links:

Genes affected

PKHD1 (HGNC:9016): (PKHD1 ciliary IPT domain containing fibrocystin/polyductin) The protein encoded by this gene is predicted to have a single transmembrane (TM)-spanning domain and multiple copies of an immunoglobulin-like plexin-transcription-factor domain. Alternative splicing results in two transcript variants encoding different isoforms. Other alternatively spliced transcripts have been described, but the full length sequences have not been determined. Several of these transcripts are predicted to encode truncated products which lack the TM and may be secreted. Mutations in this gene cause autosomal recessive polycystic kidney disease, also known as polycystic kidney and hepatic disease-1. [provided by RefSeq, Jul 2008]

PKHD1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 6-52053170-T-G is Benign according to our data. Variant chr6-52053170-T-G is described in ClinVar as [Benign]. Clinvar id is 96384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-52053170-T-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-5.03 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKHD1	NM_138694.4 link	c.2046A>C	p.Pro682Pro	synonymous_variant	Exon 21 of 67	ENST00000371117.8	NP_619639.3	P08F94-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKHD1	ENST00000371117.8 link	c.2046A>C	p.Pro682Pro	synonymous_variant	Exon 21 of 67	1	NM_138694.4	ENSP00000360158.3		P08F94-1
PKHD1	ENST00000340994.4 link	c.2046A>C	p.Pro682Pro	synonymous_variant	Exon 21 of 61	5		ENSP00000341097.4		P08F94-2

Frequencies

GnomAD3 genomes

AF:

0.0776

AC:

11811

AN:

152176

Hom.:

570

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0328

Gnomad AMI

AF:

0.0735

Gnomad AMR

AF:

0.0812

Gnomad ASJ

AF:

0.153

Gnomad EAS

AF:

0.0392

Gnomad SAS

AF:

0.0684

Gnomad FIN

AF:

0.0690

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.104

Gnomad OTH

AF:

0.102

GnomAD3 exomes

AF:

0.0874

AC:

21964

AN:

251214

Hom.:

1087

AF XY:

0.0898

AC XY:

12184

AN XY:

135750

show subpopulations

Gnomad AFR exome

AF:

0.0298

Gnomad AMR exome

AF:

0.0672

Gnomad ASJ exome

AF:

0.155

Gnomad EAS exome

AF:

0.0446

Gnomad SAS exome

AF:

0.0795

Gnomad FIN exome

AF:

0.0743

Gnomad NFE exome

AF:

0.107

Gnomad OTH exome

AF:

0.0986

GnomAD4 exome

AF:

0.0995

AC:

145440

AN:

1461790

Hom.:

7747

Cov.:

AF XY:

0.0996

AC XY:

72447

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.0324

Gnomad4 AMR exome

AF:

0.0696

Gnomad4 ASJ exome

AF:

0.157

Gnomad4 EAS exome

AF:

0.0466

Gnomad4 SAS exome

AF:

0.0801

Gnomad4 FIN exome

AF:

0.0732

Gnomad4 NFE exome

AF:

0.106

Gnomad4 OTH exome

AF:

0.0976

GnomAD4 genome

AF:

0.0777

AC:

11828

AN:

152294

Hom.:

574

Cov.:

AF XY:

0.0768

AC XY:

5723

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0329

Gnomad4 AMR

AF:

0.0811

Gnomad4 ASJ

AF:

0.153

Gnomad4 EAS

AF:

0.0393

Gnomad4 SAS

AF:

0.0685

Gnomad4 FIN

AF:

0.0690

Gnomad4 NFE

AF:

0.104

Gnomad4 OTH

AF:

0.105

Alfa

AF:

0.0791

Hom.:

269

Bravo

AF:

0.0772

Asia WGS

AF:

0.0580

AC:

203

AN:

3478

EpiCase

AF:

0.110

EpiControl

AF:

0.114

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Autosomal recessive polycystic kidney disease

Benign:3

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 11, 2017

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not specified

Benign:2

Feb 04, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Polycystic kidney disease

Benign:1

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

The PKHD1, p.Pro682Pro variant was identified in 8.6% of 121322 control alleles in the Exome Aggregation Consortium (March 14, 2016). According to ACMG guidelines for variant classification based on allele frequency, category BA1, this variant is considered benign and has not been further reviewed (Richards 2015). -

not provided

Benign:1

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Polycystic kidney disease 4

Benign:1

Jun 19, 2021

Pars Genome Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.43

DANN

Benign

0.40

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