rs841865

Variant names:

• chr1-208052564-G-A
• rs841865
• NM_025179.4:c.2857-101C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-208052564-G-A
• chr1-208052564-G-C
• chr1-208052564-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025179.4(PLXNA2):​c.2857-101C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,182,516 control chromosomes in the GnomAD database, including 19,516 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (1881 hom., cov: 32)
  • Exomes 𝑓: 0.18 (17635 hom.)
• Consequence: PLXNA2 NM_025179.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.405
• Publications: 7 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLXNA2	NM_025179.4	MANE Select	c.2857-101C>T		intron	N/A	NP_079455.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLXNA2	ENST00000367033.4	TSL:1 MANE Select	c.2857-101C>T		intron	N/A	ENSP00000356000.3

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21079 AN: 152036 Hom.: 1884 Cov.: 32

Gnomad AFR AF: 0.0380

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.157

GnomAD4 exome AF: 0.178 AC: 183064 AN: 1030362 Hom.: 17635 AF XY: 0.181 AC XY: 94138 AN XY: 520586

African (AFR) AF: 0.0307 AC: 766 AN: 24982

American (AMR) AF: 0.128 AC: 4649 AN: 36442

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 2950 AN: 19954

East Asian (EAS) AF: 0.303 AC: 11008 AN: 36390

South Asian (SAS) AF: 0.264 AC: 17434 AN: 66152

European-Finnish (FIN) AF: 0.182 AC: 7505 AN: 41190

Middle Eastern (MID) AF: 0.115 AC: 551 AN: 4802

European-Non Finnish (NFE) AF: 0.173 AC: 130367 AN: 754610

Other (OTH) AF: 0.171 AC: 7834 AN: 45840

GnomAD4 genome AF: 0.139 AC: 21082 AN: 152154 Hom.: 1881 Cov.: 32 AF XY: 0.143 AC XY: 10642 AN XY: 74374

African (AFR) AF: 0.0379 AC: 1574 AN: 41536

American (AMR) AF: 0.135 AC: 2069 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 505 AN: 3472

East Asian (EAS) AF: 0.304 AC: 1569 AN: 5158

South Asian (SAS) AF: 0.280 AC: 1349 AN: 4818

European-Finnish (FIN) AF: 0.176 AC: 1859 AN: 10588

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11577 AN: 67972

Other (OTH) AF: 0.162 AC: 342 AN: 2116

Alfa AF: 0.160 Hom.: 6683

Bravo AF: 0.131

Asia WGS AF: 0.277 AC: 961 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.7
DANN	Benign	0.37
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism (auto)

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: rs841865; hg19: chr1-208225909; COSMIC: COSV65440377;