rs781634312

Variant names:

• chr22-50277956-C-A
• rs781634312
• NM_012401.4:c.4945G>T

Your query was ambiguous. Multiple possible variants found:

• chr22-50277956-C-A
• chr22-50277956-C-T

Variant summary

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

The NM_012401.4(PLXNB2):​c.4945G>T​(p.Ala1649Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. A1649T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PLXNB2 NM_012401.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.98
• Publications: 0 publications found

Genes affected

PLXNB2 (HGNC:9104): (plexin B2) Members of the B class of plexins, such as PLXNB2 are transmembrane receptors that participate in axon guidance and cell migration in response to semaphorins (Perrot et al. (2002) [PubMed 12183458]).[supplied by OMIM, Mar 2008]

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=0.22305268).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLXNB2	NM_012401.4	c.4945G>T	p.Ala1649Ser	missense_variant	Exon 32 of 37	ENST00000359337.9	NP_036533.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLXNB2	ENST00000359337.9	c.4945G>T	p.Ala1649Ser	missense_variant	Exon 32 of 37	5	NM_012401.4	ENSP00000352288.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460596 Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0 AN XY: 726640

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52484

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111698

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.084	T;T;T;T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.51
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.52	T;.;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.22	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L;L;.;.
PhyloP100		2.0
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.1	N;N;.;N
REVEL	Benign	0.075
Sift	Uncertain	0.025	D;D;.;D
Sift4G	Benign	0.082	T;T;T;.
Polyphen		0.81	P;P;.;.
Vest4		0.30
MutPred		0.43		Gain of disorder (P = 0.056);Gain of disorder (P = 0.056);.;.;
MVP		0.25
MPC		1.2
ClinPred		0.41	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.073
gMVP		0.12
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs781634312; hg19: chr22-50716385;