dbSNP rs758935682: PLXNA2:p.Ala1841Ser (chr1-208028077-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_025179.4(PLXNA2):c.5521G>T(p.Ala1841Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A1841T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

PLXNA2
NM_025179.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.806

Publications

0 publications found

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]

PLXNA2 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD, AR Classification: LIMITED Submitted by: Ambry Genetics

PLXNA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.10580173).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025179.4. 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
	PLXNA2	NM_025179.4	MANE Select	c.5521G>T	p.Ala1841Ser	missense	Exon 31 of 32	NP_079455.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLXNA2	ENST00000367033.4	TSL:1 MANE Select	c.5521G>T	p.Ala1841Ser	missense	Exon 31 of 32	ENSP00000356000.3	O75051-1
PLXNA2	ENST00000483048.1	TSL:1	n.1557G>T		non_coding_transcript_exon	Exon 2 of 3
PLXNA2	ENST00000866341.1		c.5716G>T	p.Ala1906Ser	missense	Exon 32 of 33	ENSP00000536400.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461204

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726904

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33454

American (AMR)

AF:

0.00

AC:

AN:

44620

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39658

South Asian (SAS)

AF:

0.00

AC:

AN:

86074

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1111728

Other (OTH)

AF:

0.00

AC:

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.413

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.087

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.056

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.85

M_CAP

Benign

0.0036

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.55

PhyloP100

0.81

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-0.81

REVEL

Benign

0.10

Sift

Benign

0.39

Sift4G

Benign

0.84

Polyphen

0.0040

Vest4

0.12

MutPred

0.37

Gain of disorder (P = 0.066)

MVP

0.34

MPC

0.54

ClinPred

0.83

GERP RS

5.5

Varity_R

0.12

gMVP

0.20

Mutation Taster

=67/33

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over