NM_002487.3:c.858C>A

Variant names:

• chr15-23686360-G-T
• rs2192206
• NM_002487.3:c.858C>A

Variant summary

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

The NM_002487.3(NDN):​c.858C>A​(p.Asp286Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,444,226 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. D286D) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: NDN NM_002487.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.354
• Publications: 23 publications found

Genes affected

NDN (HGNC:7675): (necdin, MAGE family member) This intronless gene is located in the Prader-Willi syndrome deletion region. It is an imprinted gene and is expressed exclusively from the paternal allele. Studies in mouse suggest that the protein encoded by this gene may suppress growth in postmitotic neurons. [provided by RefSeq, Jul 2008]

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=0.181597).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDN	NM_002487.3	c.858C>A	p.Asp286Glu	missense_variant	Exon 1 of 1	ENST00000649030.2	NP_002478.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDN	ENST00000649030.2	c.858C>A	p.Asp286Glu	missense_variant	Exon 1 of 1		NM_002487.3	ENSP00000497916.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1444226 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 716338

African (AFR) AF: 0.00 AC: 0 AN: 32886

American (AMR) AF: 0.00 AC: 0 AN: 43058

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25080

East Asian (EAS) AF: 0.00 AC: 0 AN: 39470

South Asian (SAS) AF: 0.00 AC: 0 AN: 83806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52568

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5184

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1102684

Other (OTH) AF: 0.0000168 AC: 1 AN: 59490

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 864

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	T;T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.50	.;T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.9	L;L
PhyloP100		0.35
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.5	D;.
REVEL	Benign	0.058
Sift	Benign	0.030	D;.
Sift4G	Benign	0.13	T;.
Polyphen		0.031	B;B
Vest4		0.10
MutPred		0.40		Gain of disorder (P = 0.0511);Gain of disorder (P = 0.0511);
MVP		0.31
MPC		0.76
ClinPred		0.42	T
GERP RS		-1.8
Varity_R		0.20
gMVP		0.30
Mutation Taster		=92/8	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: rs2192206; hg19: chr15-23931507;