1-16232907-C-G

Variant names:

• chr1-16232907-C-G
• rs761874778
• NM_030907.4:c.376G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_030907.4(CPLANE2):​c.376G>C​(p.Asp126His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D126N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CPLANE2 NM_030907.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.31

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPLANE2	NM_030907.4	c.376G>C	p.Asp126His	missense_variant	Exon 3 of 5	ENST00000375599.8	NP_112169.2
CPLANE2	XM_011542126.4	c.376G>C	p.Asp126His	missense_variant	Exon 3 of 5		XP_011540428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPLANE2	ENST00000375599.8	c.376G>C	p.Asp126His	missense_variant	Exon 3 of 5	1	NM_030907.4	ENSP00000364749.2
CPLANE2	ENST00000434014.1	c.181-261G>C		intron_variant	Intron 2 of 3	5		ENSP00000406390.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Uncertain	0.56	D
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.016
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.046	D
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-0.66	T
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.014	D
Sift4G	Benign	0.077	T
Polyphen		0.12	B
Vest4		0.62
MutPred		0.67		Gain of methylation at K123 (P = 0.0513);
MVP		0.46
MPC		0.30
ClinPred		0.89	D
GERP RS		4.1
Varity_R		0.25
gMVP		0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs761874778; hg19: chr1-16559402;