16-81208497-G-C

Variant names:

• chr16-81208497-G-C
• rs6420424
• ENST00000525539.5:c.754C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000525539.5(PKD1L2):​c.754C>G​(p.Arg252Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000209 in 1,433,870 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (1 hom.)
• Consequence: PKD1L2 ENST00000525539.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.71
• Publications: 39 publications found

Genes affected

PKD1L2 (HGNC:21715): (polycystin 1 like 2 (gene/pseudogene)) This gene encodes a member of the polycystin protein family. This protein may function as a G-protein-coupled component or regulator of cation channel pores. The long isoform of this protein contains 11 transmembrane domains, a latrophilin/CL-1-like GPCR proteolytic site (GPS) domain, and a polycystin-1, lipoxygenase, alpha-toxin (PLAT) domain. Alternative splicing results in multiple transcript variants encoding distinct isoforms. This gene is a polymorphic pseudogene in humans. [provided by RefSeq, May 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14056134).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000525539.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD1L2	NR_126532.3		n.778C>G		non_coding_transcript_exon	Exon 4 of 43

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD1L2	ENST00000525539.5	TSL:1	c.754C>G	p.Arg252Gly	missense	Exon 4 of 43	ENSP00000434417.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000209 AC: 3 AN: 1433870 Hom.: 1 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 714974

African (AFR) AF: 0.00 AC: 0 AN: 33238

American (AMR) AF: 0.00 AC: 0 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25998

East Asian (EAS) AF: 0.00 AC: 0 AN: 39352

South Asian (SAS) AF: 0.00 AC: 0 AN: 85616

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53314

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 0.00000276 AC: 3 AN: 1086562

Other (OTH) AF: 0.00 AC: 0 AN: 59436

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	18
DANN	Benign	0.90
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.94	T
PhyloP100		1.7
PrimateAI	Benign	0.18	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.11
Polyphen		0.47	P
Vest4		0.30
MutPred		0.49		Gain of catalytic residue at C251 (P = 0.0566)
MVP		0.11
ClinPred		0.15	T
GERP RS		2.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs6420424; hg19: chr16-81242102;