5-137890532-C-A

Variant names:

• chr5-137890532-C-A
• rs199798746
• NM_001300921.2:c.83C>A

Variant summary

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

The NM_001300921.2(PKD2L2):​c.83C>A​(p.Thr28Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,434,762 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T28I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: PKD2L2 NM_001300921.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69
• 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.83C>A	p.Thr28Lys	missense	Exon 2 of 15	NP_001287850.1	Q9NZM6-1
	PKD2L2	NM_014386.4		c.83C>A	p.Thr28Lys	missense	Exon 2 of 14	NP_055201.2	Q9NZM6-5
	PKD2L2	NM_001258448.2		c.83C>A	p.Thr28Lys	missense	Exon 2 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.83C>A	p.Thr28Lys	missense	Exon 2 of 15	ENSP00000424725.1	Q9NZM6-1
	PKD2L2	ENST00000290431.5	TSL:1	c.83C>A	p.Thr28Lys	missense	Exon 2 of 14	ENSP00000290431.5	Q9NZM6-5
	PKD2L2	ENST00000508638.5	TSL:1	c.83C>A	p.Thr28Lys	missense	Exon 2 of 13	ENSP00000423382.1	Q9NZM6-6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.97e-7 AC: 1 AN: 1434762 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 713232

African (AFR) AF: 0.00 AC: 0 AN: 32554

American (AMR) AF: 0.00 AC: 0 AN: 42136

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25914

East Asian (EAS) AF: 0.00 AC: 0 AN: 39002

South Asian (SAS) AF: 0.00 AC: 0 AN: 80408

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53320

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5612

European-Non Finnish (NFE) AF: 9.12e-7 AC: 1 AN: 1096322

Other (OTH) AF: 0.00 AC: 0 AN: 59494

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.59	D
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.057	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		1.7
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-4.0	D
REVEL	Uncertain	0.40
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.98	D
Vest4		0.62
MutPred		0.46		Gain of ubiquitination at T28 (P = 0.0351)
MVP		0.86
MPC		0.77
ClinPred		1.0	D
GERP RS		4.9
Varity_R		0.81
gMVP		0.94
Mutation Taster		=61/39	polymorphism

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

Other links and lift over

dbSNP: rs199798746; hg19: chr5-137226221;