NM_016112.3:c.2042G>T

Variant names:

• chr10-100290485-C-A
• rs6584356
• NM_016112.3:c.2042G>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_016112.3(PKD2L1):​c.2042G>T​(p.Arg681Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0605 in 1,612,512 control chromosomes in the GnomAD database, including 3,293 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/23 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: 𝑓 0.069 (403 hom., cov: 32)
  • Exomes 𝑓: 0.060 (2890 hom.)
• Consequence: PKD2L1 NM_016112.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• Publications: 36 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0967 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016112.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD2L1	NM_016112.3	MANE Select	c.2042G>T	p.Arg681Leu	missense	Exon 13 of 16	NP_057196.2
	PKD2L1	NM_001253837.2		c.1901G>T	p.Arg634Leu	missense	Exon 13 of 16	NP_001240766.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD2L1	ENST00000318222.4	TSL:1 MANE Select	c.2042G>T	p.Arg681Leu	missense	Exon 13 of 16	ENSP00000325296.3
	PKD2L1	ENST00000528248.1	TSL:1	n.*1782G>T		non_coding_transcript_exon	Exon 13 of 16	ENSP00000436514.1
	PKD2L1	ENST00000528248.1	TSL:1	n.*1782G>T		3_prime_UTR	Exon 13 of 16	ENSP00000436514.1

Frequencies

GnomAD3 genomes AF: 0.0690 AC: 10491 AN: 152124 Hom.: 403 Cov.: 32

Gnomad AFR AF: 0.0994

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0554

Gnomad ASJ AF: 0.0662

Gnomad EAS AF: 0.0560

Gnomad SAS AF: 0.0710

Gnomad FIN AF: 0.0615

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0556

Gnomad OTH AF: 0.0731

GnomAD2 exomes AF: 0.0583 AC: 14594 AN: 250460 AF XY: 0.0578

Gnomad AFR exome AF: 0.102

Gnomad AMR exome AF: 0.0512

Gnomad ASJ exome AF: 0.0653

Gnomad EAS exome AF: 0.0524

Gnomad FIN exome AF: 0.0554

Gnomad NFE exome AF: 0.0522

Gnomad OTH exome AF: 0.0607

GnomAD4 exome AF: 0.0597 AC: 87127 AN: 1460270 Hom.: 2890 Cov.: 31 AF XY: 0.0595 AC XY: 43205 AN XY: 726562

African (AFR) AF: 0.102 AC: 3408 AN: 33448

American (AMR) AF: 0.0521 AC: 2328 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.0627 AC: 1637 AN: 26126

East Asian (EAS) AF: 0.0645 AC: 2560 AN: 39684

South Asian (SAS) AF: 0.0651 AC: 5618 AN: 86234

European-Finnish (FIN) AF: 0.0579 AC: 3057 AN: 52788

Middle Eastern (MID) AF: 0.0507 AC: 292 AN: 5764

European-Non Finnish (NFE) AF: 0.0577 AC: 64159 AN: 1111160

Other (OTH) AF: 0.0674 AC: 4068 AN: 60354

GnomAD4 genome AF: 0.0690 AC: 10498 AN: 152242 Hom.: 403 Cov.: 32 AF XY: 0.0691 AC XY: 5147 AN XY: 74450

African (AFR) AF: 0.0993 AC: 4122 AN: 41524

American (AMR) AF: 0.0554 AC: 848 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0662 AC: 230 AN: 3472

East Asian (EAS) AF: 0.0563 AC: 292 AN: 5186

South Asian (SAS) AF: 0.0708 AC: 342 AN: 4828

European-Finnish (FIN) AF: 0.0615 AC: 652 AN: 10604

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0556 AC: 3780 AN: 68014

Other (OTH) AF: 0.0724 AC: 153 AN: 2114

Alfa AF: 0.0577 Hom.: 993

Bravo AF: 0.0701

TwinsUK AF: 0.0572 AC: 212

ALSPAC AF: 0.0568 AC: 219

ESP6500AA AF: 0.0980 AC: 432

ESP6500EA AF: 0.0549 AC: 472

ExAC AF: 0.0591 AC: 7173

Asia WGS AF: 0.0850 AC: 297 AN: 3478

EpiCase AF: 0.0519

EpiControl AF: 0.0514

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.42
DANN	Uncertain	0.98
DEOGEN2	Benign	0.35	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.74	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.6	L
PhyloP100		-1.3
PrimateAI	Benign	0.18	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.18
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.019	D
Polyphen		0.046	B
Vest4		0.056
MPC		0.087
ClinPred		0.045	T
GERP RS		-6.2
Varity_R		0.11
gMVP		0.15
Mutation Taster		=83/17	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.25		Position offset: 34

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6584356; hg19: chr10-102050242; COSMIC: COSV58395841; COSMIC: COSV58395841;