NM_016112.3:c.349+4071G>A

Variant names:

• chr10-100325140-C-T
• rs646767
• NM_016112.3:c.349+4071G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016112.3(PKD2L1):​c.349+4071G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,202 control chromosomes in the GnomAD database, including 1,940 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.15 (1940 hom., cov: 33)
• Consequence: PKD2L1 NM_016112.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.885
• Publications: 9 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.328 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD2L1	NM_016112.3	MANE Select	c.349+4071G>A		intron	N/A	NP_057196.2
	PKD2L1	NM_001253837.2		c.208+4071G>A		intron	N/A	NP_001240766.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD2L1	ENST00000318222.4	TSL:1 MANE Select	c.349+4071G>A		intron	N/A	ENSP00000325296.3	Q9P0L9-1
	PKD2L1	ENST00000528248.1	TSL:1	n.*89+4071G>A		intron	N/A	ENSP00000436514.1	H0YET4
	PKD2L1	ENST00000465680.2	TSL:3	c.103+4729G>A		intron	N/A	ENSP00000434019.1	H0YDN7

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22738 AN: 152084 Hom.: 1939 Cov.: 33

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.0367

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.154

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.150 AC: 22762 AN: 152202 Hom.: 1940 Cov.: 33 AF XY: 0.150 AC XY: 11176 AN XY: 74418

African (AFR) AF: 0.178 AC: 7368 AN: 41502

American (AMR) AF: 0.117 AC: 1795 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 744 AN: 3470

East Asian (EAS) AF: 0.0368 AC: 191 AN: 5190

South Asian (SAS) AF: 0.342 AC: 1647 AN: 4820

European-Finnish (FIN) AF: 0.105 AC: 1115 AN: 10596

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9309 AN: 68004

Other (OTH) AF: 0.156 AC: 330 AN: 2114

Alfa AF: 0.150 Hom.: 1446

Bravo AF: 0.148

Asia WGS AF: 0.219 AC: 760 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.65
PhyloP100		-0.89
Mutation Taster		=100/0	polymorphism (auto)

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: rs646767; hg19: chr10-102084897;