chr10-100291312-C-G

Position:

• chr10-100291312-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016112.3(PKD2L1):​c.1996G>C​(p.Glu666Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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: 32)
• Consequence: PKD2L1 NM_016112.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.23

Genes affected

PKD2L1 (HGNC:9011): (polycystin 2 like 1, transient receptor potential cation channel) This gene encodes a member of the polycystin protein family. The encoded protein contains multiple transmembrane domains, and cytoplasmic N- and C-termini. The protein may be an integral membrane protein involved in cell-cell/matrix interactions. This protein functions as a calcium-regulated nonselective cation channel. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21145684).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKD2L1	NM_016112.3	c.1996G>C	p.Glu666Gln	missense_variant	12/16	ENST00000318222.4	NP_057196.2
PKD2L1	NM_001253837.2	c.1855G>C	p.Glu619Gln	missense_variant	12/16		NP_001240766.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKD2L1	ENST00000318222.4	c.1996G>C	p.Glu666Gln	missense_variant	12/16	1	NM_016112.3	ENSP00000325296.3
PKD2L1	ENST00000528248.1	n.*1736G>C		non_coding_transcript_exon_variant	12/16	1		ENSP00000436514.1
PKD2L1	ENST00000528248.1	n.*1736G>C		3_prime_UTR_variant	12/16	1		ENSP00000436514.1
PKD2L1	ENST00000465680.2	c.104-2834G>C		intron_variant		3		ENSP00000434019.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 04, 2024

The c.1996G>C (p.E666Q) alteration is located in exon 12 (coding exon 12) of the PKD2L1 gene. This alteration results from a G to C substitution at nucleotide position 1996, causing the glutamic acid (E) at amino acid position 666 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.34	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.22
Sift	Benign	0.065	T
Sift4G	Benign	0.081	T
Polyphen		0.41	B
Vest4		0.23
MutPred		0.20		Loss of helix (P = 0.0167);
MVP		0.64
MPC		0.11
ClinPred		0.78	D
GERP RS		4.0
Varity_R		0.10
gMVP		0.45

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: rs1848401057; hg19: chr10-102051069;