rs201038756

Variant names:

• chr1-16232262-C-T
• rs201038756
• NM_030907.4:c.563G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_030907.4(CPLANE2):​c.563G>A​(p.Arg188Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000139 in 1,609,700 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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. R188W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00014 (2 hom.)
• Consequence: CPLANE2 NM_030907.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.42
• Publications: 1 publications found

Genes affected

CPLANE2 (HGNC:28127): (ciliogenesis and planar polarity effector complex subunit 2) Predicted to enable GTP binding activity and GTPase activity. Predicted to be involved in cellular protein localization; cilium assembly; and regulation of vesicle-mediated transport. Predicted to be located in ciliary basal body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.039380014).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030907.4. 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
	CPLANE2	NM_030907.4	MANE Select	c.563G>A	p.Arg188Gln	missense	Exon 5 of 5	NP_112169.2	Q9BU20

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPLANE2	ENST00000375599.8	TSL:1 MANE Select	c.563G>A	p.Arg188Gln	missense	Exon 5 of 5	ENSP00000364749.2	Q9BU20
	CPLANE2	ENST00000945441.1		c.662G>A	p.Arg221Gln	missense	Exon 5 of 5	ENSP00000615500.1
	CPLANE2	ENST00000434014.1	TSL:5	c.*19G>A		downstream_gene	N/A	ENSP00000406390.1	H0Y6L8

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 152224 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000146 AC: 35 AN: 239074 AF XY: 0.000153

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000294

Gnomad ASJ exome AF: 0.000708

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000546

Gnomad NFE exome AF: 0.000185

Gnomad OTH exome AF: 0.000171

GnomAD4 exome AF: 0.000142 AC: 207 AN: 1457358 Hom.: 2 Cov.: 30 AF XY: 0.000148 AC XY: 107 AN XY: 725090

African (AFR) AF: 0.000149 AC: 5 AN: 33458

American (AMR) AF: 0.0000675 AC: 3 AN: 44454

Ashkenazi Jewish (ASJ) AF: 0.000729 AC: 19 AN: 26074

East Asian (EAS) AF: 0.00 AC: 0 AN: 39636

South Asian (SAS) AF: 0.000128 AC: 11 AN: 86016

European-Finnish (FIN) AF: 0.0000199 AC: 1 AN: 50304

Middle Eastern (MID) AF: 0.0115 AC: 66 AN: 5762

European-Non Finnish (NFE) AF: 0.0000738 AC: 82 AN: 1111392

Other (OTH) AF: 0.000332 AC: 20 AN: 60262

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152342 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74498

African (AFR) AF: 0.00 AC: 0 AN: 41580

American (AMR) AF: 0.000131 AC: 2 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

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

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000213 Hom.: 0

Bravo AF: 0.000121

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000165 AC: 20

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	0.080
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	19
DANN	Benign	0.81
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-0.84	T
PhyloP100		1.4
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	0.070	N
REVEL	Benign	0.063
Sift	Benign	0.43	T
Sift4G	Benign	0.60	T
Polyphen		0.025	B
Vest4		0.17
MVP		0.49
MPC		0.19
ClinPred		0.042	T
GERP RS		4.6
Varity_R		0.057
gMVP		0.41
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs201038756; hg19: chr1-16558757;