rs2784203

Variant names:

• chr6-51626758-C-G
• rs2784203
• NM_138694.4:c.11785+239G>C

Your query was ambiguous. Multiple possible variants found:

• chr6-51626758-C-G
• chr6-51626758-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_138694.4(PKHD1):​c.11785+239G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0429 in 152,156 control chromosomes in the GnomAD database, including 236 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.043 (236 hom., cov: 32)
• Consequence: PKHD1 NM_138694.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.182

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 6-51626758-C-G is Benign according to our data. Variant chr6-51626758-C-G is described in ClinVar as [Benign]. Clinvar id is 1225188.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0906 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKHD1	NM_138694.4	c.11785+239G>C		intron_variant	Intron 66 of 66	ENST00000371117.8	NP_619639.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKHD1	ENST00000371117.8	c.11785+239G>C		intron_variant	Intron 66 of 66	1	NM_138694.4	ENSP00000360158.3

Frequencies

GnomAD3 genomes AF: 0.0428 AC: 6510 AN: 152038 Hom.: 235 Cov.: 32

Gnomad AFR AF: 0.0931

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.0252

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.0201

Gnomad FIN AF: 0.0107

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0268

Gnomad OTH AF: 0.0384

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

GnomAD4 genome AF: 0.0429 AC: 6520 AN: 152156 Hom.: 236 Cov.: 32 AF XY: 0.0414 AC XY: 3078 AN XY: 74372

Gnomad4 AFR AF: 0.0930

Gnomad4 AMR AF: 0.0254

Gnomad4 ASJ AF: 0.0245

Gnomad4 EAS AF: 0.000773

Gnomad4 SAS AF: 0.0195

Gnomad4 FIN AF: 0.0107

Gnomad4 NFE AF: 0.0268

Gnomad4 OTH AF: 0.0380

Alfa AF: 0.0365 Hom.: 18

Bravo AF: 0.0470

Asia WGS AF: 0.0180 AC: 62 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 10, 2018

GeneDx

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	-0.66
CADD	Benign	12
DANN	Benign	0.60

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

Other links and lift over

dbSNP: rs2784203; hg19: chr6-51491556;