rs11243676

Variant names:

• chr9-132221380-G-A
• rs11243676
• NM_032536.4:c.858-5469G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-132221380-G-A
• chr9-132221380-G-T

Variant summary

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

The NM_032536.4(NTNG2):​c.858-5469G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0512 in 152,264 control chromosomes in the GnomAD database, including 319 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 0.051 (319 hom., cov: 32)
• Consequence: NTNG2 NM_032536.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.09
• Publications: 8 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0758 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.858-5469G>A		intron	N/A	NP_115925.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTNG2	ENST00000393229.4	TSL:1 MANE Select	c.858-5469G>A		intron	N/A	ENSP00000376921.3
	NTNG2	ENST00000946492.1		c.858-5469G>A		intron	N/A	ENSP00000616551.1
	NTNG2	ENST00000922385.1		c.858-5469G>A		intron	N/A	ENSP00000592444.1

Frequencies

GnomAD3 genomes AF: 0.0513 AC: 7801 AN: 152146 Hom.: 319 Cov.: 32

Gnomad AFR AF: 0.0117

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0276

Gnomad ASJ AF: 0.0412

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0126

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0775

Gnomad OTH AF: 0.0306

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

GnomAD4 genome AF: 0.0512 AC: 7803 AN: 152264 Hom.: 319 Cov.: 32 AF XY: 0.0514 AC XY: 3826 AN XY: 74446

African (AFR) AF: 0.0117 AC: 486 AN: 41560

American (AMR) AF: 0.0276 AC: 422 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0412 AC: 143 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5188

South Asian (SAS) AF: 0.0131 AC: 63 AN: 4824

European-Finnish (FIN) AF: 0.124 AC: 1319 AN: 10596

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0776 AC: 5275 AN: 68020

Other (OTH) AF: 0.0302 AC: 64 AN: 2116

Alfa AF: 0.0659 Hom.: 250

Bravo AF: 0.0394

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.9
DANN	Benign	0.77
PhyloP100		2.1
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: rs11243676; hg19: chr9-135096767;