NM_032536.4:c.657C>A

Variant names:

• chr9-132198409-C-A
• rs562591810
• NM_032536.4:c.657C>A

Variant summary

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

The NM_032536.4(NTNG2):​c.657C>A​(p.Phe219Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. F219F) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NTNG2 NM_032536.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.266
• Publications: 0 publications found

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]

NTNG2 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with behavioral abnormalities, absent speech, and hypotonia

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

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=0.2005181).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032536.4. 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
	NTNG2	NM_032536.4	MANE Select	c.657C>A	p.Phe219Leu	missense	Exon 3 of 8	NP_115925.2	Q96CW9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTNG2	ENST00000393229.4	TSL:1 MANE Select	c.657C>A	p.Phe219Leu	missense	Exon 3 of 8	ENSP00000376921.3	Q96CW9-1
	NTNG2	ENST00000946492.1		c.657C>A	p.Phe219Leu	missense	Exon 3 of 11	ENSP00000616551.1
	NTNG2	ENST00000922385.1		c.657C>A	p.Phe219Leu	missense	Exon 4 of 9	ENSP00000592444.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.55	D
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.60	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		-0.27
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.18
Sift	Benign	0.12	T
Sift4G	Benign	0.10	T
Polyphen		0.047	B
Vest4		0.16
MutPred		0.71		Gain of MoRF binding (P = 0.0983)
MVP		0.43
MPC		1.1
ClinPred		0.93	D
GERP RS		-2.4
Varity_R		0.38
gMVP		0.87
Mutation Taster		=55/45	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: rs562591810; hg19: chr9-135073796;