chr1-208084472-C-T

Position:

• chr1-208084472-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3 PP5_Moderate

The NM_025179.4(PLXNA2):​c.2206G>A​(p.Gly736Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PLXNA2 NM_025179.4 missense
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 4.75

Genes affected

PLXNA2 (HGNC:9100): (plexin A2) This gene encodes a member of the plexin-A family of semaphorin co-receptors. Semaphorins are a large family of secreted or membrane-bound proteins that mediate repulsive effects on axon pathfinding during nervous system development. A subset of semaphorins are recognized by plexin-A/neuropilin transmembrane receptor complexes, triggering a cellular signal transduction cascade that leads to axon repulsion. This plexin-A family member is thought to transduce signals from semaphorin-3A and -3C. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.789
• PP5: Variant 1-208084472-C-T is Pathogenic according to our data. Variant chr1-208084472-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 431732.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLXNA2	NM_025179.4	c.2206G>A	p.Gly736Ser	missense_variant	10/32	ENST00000367033.4	NP_079455.3
PLXNA2	XM_005273164.4	c.2251G>A	p.Gly751Ser	missense_variant	10/33		XP_005273221.1
PLXNA2	XM_005273165.5	c.2251G>A	p.Gly751Ser	missense_variant	10/31		XP_005273222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLXNA2	ENST00000367033.4	c.2206G>A	p.Gly736Ser	missense_variant	10/32	1	NM_025179.4	ENSP00000356000	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

atypical cerebral palsy Pathogenic:1

Likely pathogenic, criteria provided, single submitter

research

TIDEX, University of British Columbia

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.016	T
MetaRNN	Pathogenic	0.79	D
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.8	L
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.22
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.30	T
Polyphen		0.99	D
Vest4		0.83
MutPred		0.30		Gain of disorder (P = 0.0909);
MVP		0.51
MPC		0.40
ClinPred		0.80	D
GERP RS		5.7
Varity_R		0.29
gMVP		0.72

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: rs1553277591; hg19: chr1-208257817;