1-208028006-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6

The NM_025179.4(PLXNA2):​c.5589+3G>A variant causes a splice region, intron 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. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

PLXNA2
NM_025179.4 splice_region, intron

Scores

2
Splicing: ADA: 0.00005741
2

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.126
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP6
Variant 1-208028006-C-T is Benign according to our data. Variant chr1-208028006-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3030257.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PLXNA2NM_025179.4 linkuse as main transcriptc.5589+3G>A splice_region_variant, intron_variant ENST00000367033.4 NP_079455.3 O75051-1
PLXNA2XM_005273164.4 linkuse as main transcriptc.5829+3G>A splice_region_variant, intron_variant XP_005273221.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PLXNA2ENST00000367033.4 linkuse as main transcriptc.5589+3G>A splice_region_variant, intron_variant 1 NM_025179.4 ENSP00000356000.3 O75051-1
PLXNA2ENST00000483048.1 linkuse as main transcriptn.1625+3G>A splice_region_variant, intron_variant 1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

PLXNA2-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesNov 23, 2021This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.42
CADD
Benign
7.8
DANN
Benign
0.58

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000057
dbscSNV1_RF
Benign
0.034
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1664390198; hg19: chr1-208201351; API