NM_030907.4:c.668G>A

Variant names:

• chr1-16232157-C-T
• NM_030907.4:c.668G>A

Variant summary

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

The NM_030907.4(CPLANE2):​c.668G>A​(p.Gly223Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CPLANE2 NM_030907.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.55

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.668G>A	p.Gly223Glu	missense_variant	Exon 5 of 5	ENST00000375599.8	NP_112169.2
CPLANE2	XM_011542126.4	c.*55G>A		3_prime_UTR_variant	Exon 5 of 5		XP_011540428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPLANE2	ENST00000375599.8	c.668G>A	p.Gly223Glu	missense_variant	Exon 5 of 5	1	NM_030907.4	ENSP00000364749.2
CPLANE2	ENST00000434014.1	c.*124G>A		downstream_gene_variant		5		ENSP00000406390.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 27, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.668G>A (p.G223E) alteration is located in exon 5 (coding exon 5) of the RSG1 gene. This alteration results from a G to A substitution at nucleotide position 668, causing the glycine (G) at amino acid position 223 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.028	T
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.86	N
REVEL	Uncertain	0.32
Sift	Benign	0.73	T
Sift4G	Benign	0.35	T
Polyphen		0.78	P
Vest4		0.86
MutPred		0.70		Loss of catalytic residue at A222 (P = 0.0411);
MVP		0.54
MPC		0.49
ClinPred		0.95	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.26
gMVP		0.86

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-16558652;