1-16232952-G-T

Variant names:

• chr1-16232952-G-T
• NM_030907.4:c.331C>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_030907.4(CPLANE2):​c.331C>A​(p.Arg111Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. R111C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CPLANE2 NM_030907.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.92

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.806

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPLANE2	NM_030907.4	c.331C>A	p.Arg111Ser	missense_variant	Exon 3 of 5	ENST00000375599.8	NP_112169.2
CPLANE2	XM_011542126.4	c.331C>A	p.Arg111Ser	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.331C>A	p.Arg111Ser	missense_variant	Exon 3 of 5	1	NM_030907.4	ENSP00000364749.2
CPLANE2	ENST00000434014.1	c.181-306C>A		intron_variant	Intron 2 of 3	5		ENSP00000406390.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461868 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727238

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.37	T
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.79	T
M_CAP	Uncertain	0.095	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Benign	-0.49	T
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.50
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.12	T
Polyphen		0.50	P
Vest4		0.76
MutPred		0.60		Loss of sheet (P = 0.0228);
MVP		0.57
MPC		0.69
ClinPred		0.95	D
GERP RS		4.8
Varity_R		0.43
gMVP		0.65

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: chr1-16559447;