chr9-132198125-C-CT

Position:

• chr9-132198125-C-CT

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_032536.4(NTNG2):​c.376dup​(p.Ser126PhefsTer241) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NTNG2 NM_032536.4 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:2
• Conservation: PhyloP100: 8.00

Genes affected

NTNG2 (HGNC:14288): (netrin G2) Predicted to be involved in several processes, including basement membrane assembly; cell morphogenesis involved in differentiation; and regulation of cell projection organization. Located in Flemming body; intercellular bridge; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 9-132198125-C-CT is Pathogenic according to our data. Variant chr9-132198125-C-CT is described in ClinVar as [Pathogenic]. Clinvar id is 690370.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTNG2	NM_032536.4	c.376dup	p.Ser126PhefsTer241	frameshift_variant	3/8	ENST00000393229.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTNG2	ENST00000393229.4	c.376dup	p.Ser126PhefsTer241	frameshift_variant	3/8	1	NM_032536.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

Submissions by phenotype

Neurodevelopmental disorder with behavioral abnormalities, absent speech, and hypotonia Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Dec 23, 2019

- -

Areflexia;C0557874:Global developmental delay;C0562479:Stereotypical hand wringing;C1858120:Generalized hypotonia Pathogenic:1

Pathogenic, no assertion criteria provided

clinical testing

Clinical Genomics Unit, Sheba Medical Center

Aug 19, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs1589441428; hg19: chr9-135073512;