10-100288427-C-T

Variant names:

• chr10-100288427-C-T
• rs142439136
• NM_016112.3:c.2387G>A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_016112.3(PKD2L1):​c.2387G>A​(p.Arg796His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00139 in 1,612,830 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (23 hom.)
• Consequence: PKD2L1 NM_016112.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.74
• Publications: 7 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0033938587).
• BP6: Variant 10-100288427-C-T is Benign according to our data. Variant chr10-100288427-C-T is described in ClinVar as Benign. ClinVar VariationId is 720318.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 161 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD2L1	NM_016112.3	MANE Select	c.2387G>A	p.Arg796His	missense	Exon 16 of 16	NP_057196.2
	PKD2L1	NM_001253837.2		c.2246G>A	p.Arg749His	missense	Exon 16 of 16	NP_001240766.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD2L1	ENST00000318222.4	TSL:1 MANE Select	c.2387G>A	p.Arg796His	missense	Exon 16 of 16	ENSP00000325296.3	Q9P0L9-1
	PKD2L1	ENST00000528248.1	TSL:1	n.*2127G>A		non_coding_transcript_exon	Exon 16 of 16	ENSP00000436514.1	H0YET4
	PKD2L1	ENST00000528248.1	TSL:1	n.*2127G>A		3_prime_UTR	Exon 16 of 16	ENSP00000436514.1	H0YET4

Frequencies

GnomAD3 genomes AF: 0.00109 AC: 166 AN: 152178 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0114

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00110

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00232 AC: 582 AN: 251344 AF XY: 0.00308

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000954

Gnomad ASJ exome AF: 0.00169

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.00118

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00142 AC: 2077 AN: 1460534 Hom.: 23 Cov.: 28 AF XY: 0.00186 AC XY: 1349 AN XY: 726694

African (AFR) AF: 0.000120 AC: 4 AN: 33444

American (AMR) AF: 0.00107 AC: 48 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00168 AC: 44 AN: 26130

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.0127 AC: 1093 AN: 86208

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53416

Middle Eastern (MID) AF: 0.0142 AC: 82 AN: 5764

European-Non Finnish (NFE) AF: 0.000617 AC: 685 AN: 1110800

Other (OTH) AF: 0.00194 AC: 117 AN: 60352

GnomAD4 genome AF: 0.00106 AC: 161 AN: 152296 Hom.: 0 Cov.: 32 AF XY: 0.00124 AC XY: 92 AN XY: 74462

African (AFR) AF: 0.000192 AC: 8 AN: 41568

American (AMR) AF: 0.000719 AC: 11 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.0108 AC: 52 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00110 AC: 75 AN: 68028

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00127 Hom.: 0

Bravo AF: 0.000929

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00116 AC: 10

ExAC AF: 0.00237 AC: 288

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00240

EpiControl AF: 0.00166

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.17
DANN	Benign	0.60
DEOGEN2	Benign	0.083	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0045	N
LIST_S2	Benign	0.37	T
MetaRNN	Benign	0.0034	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-3.7
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.075
Sift	Benign	0.55	T
Sift4G	Benign	0.24	T
Polyphen		0.0	B
Vest4		0.014
MVP		0.26
MPC		0.082
ClinPred		0.011	T
GERP RS		-6.6
Varity_R		0.024
gMVP		0.23
Mutation Taster		=99/1	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: rs142439136; hg19: chr10-102048184; COSMIC: COSV58394378; COSMIC: COSV58394378;