NM_001300921.2:c.452T>C

Variant names:

• chr5-137894537-T-C
• rs746706437
• NM_001300921.2:c.452T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001300921.2(PKD2L2):​c.452T>C​(p.Met151Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000242 in 1,613,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M151I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: PKD2L2 NM_001300921.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.84
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16960564).

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.452T>C	p.Met151Thr	missense	Exon 4 of 15	NP_001287850.1	Q9NZM6-1
	PKD2L2	NM_014386.4		c.452T>C	p.Met151Thr	missense	Exon 4 of 14	NP_055201.2	Q9NZM6-5
	PKD2L2	NM_001258448.2		c.452T>C	p.Met151Thr	missense	Exon 4 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.452T>C	p.Met151Thr	missense	Exon 4 of 15	ENSP00000424725.1	Q9NZM6-1
	PKD2L2	ENST00000290431.5	TSL:1	c.452T>C	p.Met151Thr	missense	Exon 4 of 14	ENSP00000290431.5	Q9NZM6-5
	PKD2L2	ENST00000508638.5	TSL:1	c.452T>C	p.Met151Thr	missense	Exon 4 of 13	ENSP00000423382.1	Q9NZM6-6

Frequencies

GnomAD3 genomes AF: 0.0000328 AC: 5 AN: 152226 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000281 AC: 7 AN: 249418 AF XY: 0.00000739

Gnomad AFR exome AF: 0.000258

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000233 AC: 34 AN: 1461000 Hom.: 0 Cov.: 30 AF XY: 0.0000165 AC XY: 12 AN XY: 726902

African (AFR) AF: 0.000239 AC: 8 AN: 33456

American (AMR) AF: 0.0000447 AC: 2 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

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

European-Non Finnish (NFE) AF: 0.0000207 AC: 23 AN: 1111254

Other (OTH) AF: 0.0000166 AC: 1 AN: 60364

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152226 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74368

African (AFR) AF: 0.000121 AC: 5 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68046

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000658 Hom.: 0

Bravo AF: 0.0000416

ExAC AF: 0.0000166 AC: 2

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	0.13
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Uncertain	0.56	D
Eigen	Benign	-0.10
Eigen_PC	Benign	-0.035
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.57	T
M_CAP	Uncertain	0.087	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	1.3	L
PhyloP100		4.8
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.27
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.017	D
Polyphen		0.018	B
Vest4		0.40
MVP		0.82
MPC		0.23
ClinPred		0.091	T
GERP RS		4.4
Varity_R		0.48
gMVP		0.80
Mutation Taster		=76/24	polymorphism

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: rs746706437; hg19: chr5-137230226; COSMIC: COSV51794582;