9-132198490-C-T

Variant names:

• chr9-132198490-C-T
• rs3824574
• NM_032536.4:c.738C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_032536.4(NTNG2):​c.738C>T​(p.Phe246Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 1,612,962 control chromosomes in the GnomAD database, including 81,327 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (6557 hom., cov: 33)
  • Exomes 𝑓: 0.32 (74770 hom.)
• Consequence: NTNG2 NM_032536.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.74
• Publications: 14 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 9-132198490-C-T is Benign according to our data. Variant chr9-132198490-C-T is described in ClinVar as Benign. ClinVar VariationId is 1222197.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.74 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

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.738C>T	p.Phe246Phe	synonymous	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.738C>T	p.Phe246Phe	synonymous	Exon 3 of 8	ENSP00000376921.3	Q96CW9-1
	NTNG2	ENST00000946492.1		c.738C>T	p.Phe246Phe	synonymous	Exon 3 of 11	ENSP00000616551.1
	NTNG2	ENST00000922385.1		c.738C>T	p.Phe246Phe	synonymous	Exon 4 of 9	ENSP00000592444.1

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43606 AN: 152074 Hom.: 6560 Cov.: 33

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.297

GnomAD2 exomes AF: 0.320 AC: 79560 AN: 248472 AF XY: 0.324

Gnomad AFR exome AF: 0.193

Gnomad AMR exome AF: 0.295

Gnomad ASJ exome AF: 0.374

Gnomad EAS exome AF: 0.356

Gnomad FIN exome AF: 0.390

Gnomad NFE exome AF: 0.318

Gnomad OTH exome AF: 0.320

GnomAD4 exome AF: 0.318 AC: 464708 AN: 1460770 Hom.: 74770 Cov.: 58 AF XY: 0.320 AC XY: 232336 AN XY: 726710

African (AFR) AF: 0.197 AC: 6611 AN: 33476

American (AMR) AF: 0.295 AC: 13171 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.373 AC: 9741 AN: 26134

East Asian (EAS) AF: 0.383 AC: 15194 AN: 39698

South Asian (SAS) AF: 0.334 AC: 28786 AN: 86256

European-Finnish (FIN) AF: 0.384 AC: 20095 AN: 52362

Middle Eastern (MID) AF: 0.344 AC: 1985 AN: 5768

European-Non Finnish (NFE) AF: 0.315 AC: 350508 AN: 1111976

Other (OTH) AF: 0.308 AC: 18617 AN: 60378

GnomAD4 genome AF: 0.287 AC: 43616 AN: 152192 Hom.: 6557 Cov.: 33 AF XY: 0.290 AC XY: 21595 AN XY: 74412

African (AFR) AF: 0.200 AC: 8305 AN: 41540

American (AMR) AF: 0.275 AC: 4202 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 1243 AN: 3470

East Asian (EAS) AF: 0.358 AC: 1850 AN: 5162

South Asian (SAS) AF: 0.319 AC: 1540 AN: 4830

European-Finnish (FIN) AF: 0.395 AC: 4186 AN: 10602

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.314 AC: 21353 AN: 67974

Other (OTH) AF: 0.295 AC: 625 AN: 2116

Alfa AF: 0.310 Hom.: 33332

Bravo AF: 0.276

Asia WGS AF: 0.322 AC: 1117 AN: 3478

EpiCase AF: 0.319

EpiControl AF: 0.334

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Neurodevelopmental disorder with behavioral abnormalities, absent speech, and hypotonia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	12
DANN	Benign	0.80
PhyloP100		2.7
Mutation Taster		=99/1	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: rs3824574; hg19: chr9-135073877; COSMIC: COSV62364425;