rs1533949

Positions:

• chr2-36553877-G-A
• chr2-36553877-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005102.3(FEZ2):​c.1046-698C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 152,012 control chromosomes in the GnomAD database, including 7,905 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 0.32 (7905 hom., cov: 32)
• Consequence: FEZ2 NM_005102.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.350

Genes affected

FEZ2 (HGNC:3660): (fasciculation and elongation protein zeta 2) This gene is an ortholog of the C. elegans unc-76 gene, which is necessary for normal axonal bundling and elongation within axon bundles. Other orthologs include the rat gene that encodes zygin II, which can bind to synaptotagmin. [provided by RefSeq, Jul 2008]

FEZ2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FEZ2	NM_005102.3	c.1046-698C>T		intron_variant		ENST00000405912.8	NP_005093.2
FEZ2	NM_001042548.2	c.1127-698C>T		intron_variant			NP_001036013.1
FEZ2	XR_244972.4	n.996-698C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FEZ2	ENST00000405912.8	c.1046-698C>T		intron_variant		1	NM_005102.3	ENSP00000385112.3

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48273 AN: 151894 Hom.: 7904 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.344

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.318 AC: 48286 AN: 152012 Hom.: 7905 Cov.: 32 AF XY: 0.318 AC XY: 23657 AN XY: 74294

Gnomad4 AFR AF: 0.287

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.467

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.392

Gnomad4 NFE AF: 0.344

Gnomad4 OTH AF: 0.343

Alfa AF: 0.305 Hom.: 3663

Bravo AF: 0.308

Asia WGS AF: 0.219 AC: 765 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.9
DANN	Benign	0.65

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: rs1533949; hg19: chr2-36781020;