12-44590169-T-G

Position:

• chr12-44590169-T-G

Variant summary

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

The NM_001145108.2(NELL2):​c.1663+17000A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.843 in 151,998 control chromosomes in the GnomAD database, including 54,425 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 0.84 (54425 hom., cov: 33)
• Consequence: NELL2 NM_001145108.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.263

Genes affected

NELL2 (HGNC:7751): (neural EGFL like 2) The protein encoded by this gene is a glycoprotein containing several von Willebrand factor C domains and epidermal growth factor (EGF)-like domains. The encoded protein acts as a homotrimer and is found in the cytoplasm. Several variants encoding a few different isoforms exist, and at least one isoform appears to be a secreted protein. Studies in mouse suggest that this protein plays a role in neural cell growth and differentiation as well as in oncogenesis. [provided by RefSeq, Feb 2009]

NELL2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NELL2	NM_001145108.2	c.1663+17000A>C		intron_variant		ENST00000429094.7	NP_001138580.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NELL2	ENST00000429094.7	c.1663+17000A>C		intron_variant		1	NM_001145108.2	ENSP00000390680.2

Frequencies

GnomAD3 genomes AF: 0.843 AC: 128005 AN: 151882 Hom.: 54368 Cov.: 33

Gnomad AFR AF: 0.934

Gnomad AMI AF: 0.794

Gnomad AMR AF: 0.813

Gnomad ASJ AF: 0.740

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.930

Gnomad FIN AF: 0.854

Gnomad MID AF: 0.814

Gnomad NFE AF: 0.780

Gnomad OTH AF: 0.834

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

GnomAD4 genome AF: 0.843 AC: 128119 AN: 151998 Hom.: 54425 Cov.: 33 AF XY: 0.848 AC XY: 63000 AN XY: 74316

Gnomad4 AFR AF: 0.935

Gnomad4 AMR AF: 0.813

Gnomad4 ASJ AF: 0.740

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.930

Gnomad4 FIN AF: 0.854

Gnomad4 NFE AF: 0.780

Gnomad4 OTH AF: 0.836

Alfa AF: 0.804 Hom.: 22318

Bravo AF: 0.841

Asia WGS AF: 0.952 AC: 3304 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.8
DANN	Benign	0.55

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: rs7299371; hg19: chr12-44983952;