5-137906426-C-T

Variant names:

• chr5-137906426-C-T
• NM_001300921.2:c.967C>T

Variant summary

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

The NM_001300921.2(PKD2L2):​c.967C>T​(p.Leu323Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PKD2L2 NM_001300921.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.296
• Publications: 0 publications found

Genes affected

PKD2L2 (HGNC:9012): (polycystin 2 like 2, transient receptor potential cation channel) Predicted to enable calcium channel activity. Predicted to be involved in detection of mechanical stimulus. Predicted to be integral component of membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001300921.2. 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
	PKD2L2	NM_001300921.2	MANE Select	c.967C>T	p.Leu323Phe	missense	Exon 6 of 15	NP_001287850.1	Q9NZM6-1
	PKD2L2	NM_014386.4		c.967C>T	p.Leu323Phe	missense	Exon 6 of 14	NP_055201.2	Q9NZM6-5
	PKD2L2	NM_001258448.2		c.967C>T	p.Leu323Phe	missense	Exon 6 of 15	NP_001245377.1	Q9NZM6-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD2L2	ENST00000508883.6	TSL:1 MANE Select	c.967C>T	p.Leu323Phe	missense	Exon 6 of 15	ENSP00000424725.1	Q9NZM6-1
	PKD2L2	ENST00000290431.5	TSL:1	c.967C>T	p.Leu323Phe	missense	Exon 6 of 14	ENSP00000290431.5	Q9NZM6-5
	PKD2L2	ENST00000508638.5	TSL:1	c.967C>T	p.Leu323Phe	missense	Exon 6 of 13	ENSP00000423382.1	Q9NZM6-6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 24

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.55	D
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.073	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Uncertain	-0.013	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.30
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.45
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.010	D
Polyphen		0.99	D
Vest4		0.46
MutPred		0.54		Gain of MoRF binding (P = 0.238)
MVP		0.78
MPC		0.79
ClinPred		0.92	D
GERP RS		5.3
Varity_R		0.64
gMVP		0.54
Mutation Taster		=59/41	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

hg19: chr5-137242115;