1-16232526-T-G

Variant names:

• chr1-16232526-T-G
• NM_030907.4:c.511A>C
• CPLANE2 p.Met171Leu

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030907.4(CPLANE2):​c.511A>C​(p.Met171Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CPLANE2 NM_030907.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.246
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1977765).

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.511A>C	p.Met171Leu	missense	Exon 4 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.511A>C	p.Met171Leu	missense	Exon 4 of 5	ENSP00000364749.2	Q9BU20
	CPLANE2	ENST00000945441.1		c.511A>C	p.Met171Leu	missense	Exon 4 of 5	ENSP00000615500.1
	CPLANE2	ENST00000434014.1	TSL:5	c.301A>C	p.Met101Leu	missense	Exon 3 of 4	ENSP00000406390.1	H0Y6L8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	12
DANN	Benign	0.91
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.25
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.12	N
REVEL	Benign	0.073
Sift	Benign	0.27	T
Sift4G	Benign	0.28	T
Varity_R		0.12
gMVP		0.48
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-16559021;