16-81179773-A-T

Variant names:

• chr16-81179773-A-T
• rs4889261
• ENST00000525539.5:c.2132T>A

Variant summary

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

The ENST00000525539.5(PKD1L2):​c.2132T>A​(p.Leu711Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000684 in 1,461,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 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: 31)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: PKD1L2 ENST00000525539.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.75
• Publications: 32 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=0.13300118).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD1L2	NR_126532.3		n.2147T>A		non_coding_transcript_exon	Exon 13 of 43

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD1L2	ENST00000525539.5	TSL:1	c.2132T>A	p.Leu711Gln	missense	Exon 13 of 43	ENSP00000434417.1
	PKD1L2	ENST00000533478.5	TSL:1	c.77T>A	p.Leu26Gln	missense	Exon 2 of 32	ENSP00000434644.1
	PKD1L2	ENST00000531391.5	TSL:1	c.77T>A	p.Leu26Gln	missense	Exon 2 of 7	ENSP00000436309.1	Q7Z442-4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461706 Hom.: 0 Cov.: 58 AF XY: 0.00000550 AC XY: 4 AN XY: 727138

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000899 AC: 10 AN: 1111914

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	18
DANN	Benign	0.93
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.068	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.42	T
PhyloP100		3.8
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.44	N
REVEL	Benign	0.19
Polyphen		0.087	B
Vest4		0.26
MutPred		0.35		Gain of disorder (P = 0.0218)
MVP		0.34
MPC		0.00061
ClinPred		0.94	D
GERP RS		5.0
Mutation Taster		=76/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4889261; hg19: chr16-81213378;