rs11018874

Positions:

• chr11-90142269-G-A

Variant summary

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

The NM_005467.4(NAALAD2):​c.195-5061G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 152,026 control chromosomes in the GnomAD database, including 1,288 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 0.10 (1288 hom., cov: 32)
• Consequence: NAALAD2 NM_005467.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.230

Genes affected

NAALAD2 (HGNC:14526): (N-acetylated alpha-linked acidic dipeptidase 2) This gene is a member of the N-acetylated alpha-linked acidic dipeptidase (NAALADase) gene family. The representative member of this family is the gene encoding human prostate-specific membrane antigen (PSM), which is a marker of prostatic carcinomas and is the first to be shown to possess NAALADase activity. NAALADase cleaves N-acetyl-L-aspartate-L-glutamate (NAAG), which is a neuropeptide expressed both in the central nervous systems and in the periphery and is thought to function as a neurotransmitter. The product of this gene is a type II integral membrane protein. Transient transfection of this gene confers both NAALADase and dipetidyl peptidase IV activities to mammalian cells. This gene is highly expressed in ovary and testis as well as within discrete brain areas. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

NAALAD2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAALAD2	NM_005467.4	c.195-5061G>A		intron_variant		ENST00000534061.6	NP_005458.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAALAD2	ENST00000534061.6	c.195-5061G>A		intron_variant		1	NM_005467.4	ENSP00000432481.1

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15260 AN: 151908 Hom.: 1280 Cov.: 32

Gnomad AFR AF: 0.0214

Gnomad AMI AF: 0.0484

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.0524

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0935

Gnomad OTH AF: 0.0954

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

GnomAD4 genome AF: 0.100 AC: 15273 AN: 152026 Hom.: 1288 Cov.: 32 AF XY: 0.108 AC XY: 8038 AN XY: 74326

Gnomad4 AFR AF: 0.0213

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.0524

Gnomad4 EAS AF: 0.245

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.0935

Gnomad4 OTH AF: 0.0939

Alfa AF: 0.0984 Hom.: 1110

Bravo AF: 0.107

Asia WGS AF: 0.142 AC: 496 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.1
DANN	Benign	0.47

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: rs11018874; hg19: chr11-89875437;