rs2078087

Positions:

• chr1-183389270-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015039.4(NMNAT2):​c.85+28913G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,168 control chromosomes in the GnomAD database, including 2,065 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 0.16 (2065 hom., cov: 32)
• Consequence: NMNAT2 NM_015039.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.702

Genes affected

NMNAT2 (HGNC:16789): (nicotinamide nucleotide adenylyltransferase 2) This gene product belongs to the nicotinamide mononucleotide adenylyltransferase (NMNAT) enzyme family, members of which catalyze an essential step in NAD (NADP) biosynthetic pathway. Unlike the other human family member, which is localized to the nucleus, and is ubiquitously expressed; this enzyme is cytoplasmic, and is predominantly expressed in the brain. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NMNAT2	NM_015039.4	c.85+28913G>A		intron_variant		ENST00000287713.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NMNAT2	ENST00000287713.7	c.85+28913G>A		intron_variant		1	NM_015039.4	P1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23826 AN: 152050 Hom.: 2052 Cov.: 32

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.0974

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.157 AC: 23875 AN: 152168 Hom.: 2065 Cov.: 32 AF XY: 0.158 AC XY: 11782 AN XY: 74408

Gnomad4 AFR AF: 0.228

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.238

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.0974

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.140

Alfa AF: 0.121 Hom.: 2065

Bravo AF: 0.162

Asia WGS AF: 0.248 AC: 863 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2078087; hg19: chr1-183358405;