rs750905072

Variant names:

• chr1-16232272-C-A
• NM_030907.4:c.553G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-16232272-C-A
• chr1-16232272-C-T

Variant summary

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

The NM_030907.4(CPLANE2):​c.553G>T​(p.Val185Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,456,298 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. V185M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CPLANE2 NM_030907.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.49

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, 0.794

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPLANE2	NM_030907.4	c.553G>T	p.Val185Leu	missense_variant	Exon 5 of 5	ENST00000375599.8	NP_112169.2
CPLANE2	XM_011542126.4	c.564G>T	p.Thr188Thr	synonymous_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.553G>T	p.Val185Leu	missense_variant	Exon 5 of 5	1	NM_030907.4	ENSP00000364749.2
CPLANE2	ENST00000434014.1	c.*9G>T		downstream_gene_variant		5		ENSP00000406390.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456298 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 724540

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.46	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.85	D
M_CAP	Uncertain	0.086	D
MetaRNN	Pathogenic	0.79	D
MetaSVM	Uncertain	-0.13	T
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.48
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.023	D
Polyphen		0.98	D
Vest4		0.71
MutPred		0.59		Gain of disorder (P = 0.2095);
MVP		0.71
MPC		0.30
ClinPred		0.92	D
GERP RS		5.5
Varity_R		0.33
gMVP		0.83

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: chr1-16558767;