NM_030907.4:c.632G>A

Variant names:

• chr1-16232193-C-T
• rs776318544
• NM_030907.4:c.632G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_030907.4(CPLANE2):​c.632G>A​(p.Arg211Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000178 in 1,460,500 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000018 (1 hom.)
• Consequence: CPLANE2 NM_030907.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.55
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34740347).

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.632G>A	p.Arg211Gln	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.632G>A	p.Arg211Gln	missense	Exon 5 of 5	ENSP00000364749.2	Q9BU20
	CPLANE2	ENST00000945441.1		c.731G>A	p.Arg244Gln	missense	Exon 5 of 5	ENSP00000615500.1
	CPLANE2	ENST00000434014.1	TSL:5	c.*88G>A		downstream_gene	N/A	ENSP00000406390.1	H0Y6L8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000163 AC: 4 AN: 245642 AF XY: 0.0000150

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000272

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.0000178 AC: 26 AN: 1460500 Hom.: 1 Cov.: 30 AF XY: 0.0000138 AC XY: 10 AN XY: 726626

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26092

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86210

European-Finnish (FIN) AF: 0.0000191 AC: 1 AN: 52390

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1111836

Other (OTH) AF: 0.000166 AC: 10 AN: 60350

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000330 AC: 4

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000164

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	0.12
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.016	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.85	T
PhyloP100		3.5
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.49	N
REVEL	Benign	0.18
Sift	Benign	0.070	T
Sift4G	Uncertain	0.023	D
Polyphen		1.0	D
Vest4		0.19
MVP		0.66
MPC		0.65
ClinPred		0.69	D
GERP RS		5.5
Varity_R		0.11
gMVP		0.47
Mutation Taster		=76/24	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: rs776318544; hg19: chr1-16558688;