rs2022013

Variant names:

• chr1-183384718-C-T
• rs2022013
• NM_015039.4:c.85+33465G>A

Variant summary

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

The NM_015039.4(NMNAT2):​c.85+33465G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 152,046 control chromosomes in the GnomAD database, including 21,188 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 0.51 (21188 hom., cov: 32)
• Consequence: NMNAT2 NM_015039.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.995
• Publications: 19 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NMNAT2	NM_015039.4	c.85+33465G>A		intron_variant	Intron 1 of 10	ENST00000287713.7	NP_055854.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NMNAT2	ENST00000287713.7	c.85+33465G>A		intron_variant	Intron 1 of 10	1	NM_015039.4	ENSP00000287713.6

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77856 AN: 151928 Hom.: 21180 Cov.: 32

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.653

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.548

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

GnomAD4 genome AF: 0.512 AC: 77886 AN: 152046 Hom.: 21188 Cov.: 32 AF XY: 0.514 AC XY: 38208 AN XY: 74320

African (AFR) AF: 0.320 AC: 13267 AN: 41464

American (AMR) AF: 0.565 AC: 8621 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.634 AC: 2201 AN: 3472

East Asian (EAS) AF: 0.653 AC: 3381 AN: 5176

South Asian (SAS) AF: 0.456 AC: 2195 AN: 4816

European-Finnish (FIN) AF: 0.638 AC: 6740 AN: 10572

Middle Eastern (MID) AF: 0.592 AC: 173 AN: 292

European-Non Finnish (NFE) AF: 0.583 AC: 39619 AN: 67962

Other (OTH) AF: 0.554 AC: 1168 AN: 2110

Alfa AF: 0.562 Hom.: 83478

Bravo AF: 0.501

Asia WGS AF: 0.545 AC: 1894 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.18
DANN	Benign	0.40
PhyloP100		-0.99
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: rs2022013; hg19: chr1-183353853; COSMIC: COSV55078767;