12-663458-G-T

Position:

• chr12-663458-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000543884.2(NINJ2-AS1):​n.351G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,368 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NINJ2-AS1 ENST00000543884.2 non_coding_transcript_exon
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.47

Genes affected

NINJ2-AS1 (HGNC:40405): (NINJ2 antisense RNA 1)

NINJ2 (HGNC:7825): (ninjurin 2) The protein encoded by this gene belongs to the ninjurin (for nerve injury induced) family. It is a cell surface adhesion protein that is upregulated in Schwann cells surrounding the distal segment of injured nerve, and promotes neurite outgrowth, thus may have a role in nerve regeneration after nerve injury. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15262711).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NINJ2	NM_016533.6			upstream_gene_variant		ENST00000305108.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NINJ2-AS1	ENST00000543884.2	n.351G>T		non_coding_transcript_exon_variant	3/3	3
NINJ2	ENST00000662884.1	c.41C>A	p.Pro14Gln	missense_variant	1/4
NINJ2-AS1	ENST00000662519.1	n.594G>T		non_coding_transcript_exon_variant	3/3
NINJ2	ENST00000305108.10			upstream_gene_variant		1	NM_016533.6	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460368 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726512

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 30, 2024

The c.41C>A (p.P14Q) alteration is located in exon 1 (coding exon 1) of the NINJ2 gene. This alteration results from a C to A substitution at nucleotide position 41, causing the proline (P) at amino acid position 14 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	11
DANN	Uncertain	0.98
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.12
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.070	T
Vest4		0.22
MutPred		0.20		Loss of loop (P = 0.0031);
MVP		0.63
MPC		0.59
ClinPred		0.99	D
GERP RS		1.9
gMVP		0.23

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: rs775486550; hg19: chr12-772624;