12-44590169-T-G

Variant names:

• chr12-44590169-T-G
• rs7299371
• NM_001145108.2:c.1663+17000A>C

Variant summary

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

The NM_001145107.2(NELL2):​c.1813+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_001145107.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.263
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145107.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NELL2	NM_001145108.2	MANE Select	c.1663+17000A>C		intron	N/A	NP_001138580.1
	NELL2	NM_001145107.2		c.1813+17000A>C		intron	N/A	NP_001138579.1
	NELL2	NM_001145110.2		c.1732+17000A>C		intron	N/A	NP_001138582.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NELL2	ENST00000429094.7	TSL:1 MANE Select	c.1663+17000A>C		intron	N/A	ENSP00000390680.2
	NELL2	ENST00000452445.6	TSL:1	c.1663+17000A>C		intron	N/A	ENSP00000394612.2
	NELL2	ENST00000395487.6	TSL:1	c.1660+17000A>C		intron	N/A	ENSP00000378866.2

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

African (AFR) AF: 0.935 AC: 38770 AN: 41484

American (AMR) AF: 0.813 AC: 12411 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.740 AC: 2568 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5171 AN: 5178

South Asian (SAS) AF: 0.930 AC: 4480 AN: 4818

European-Finnish (FIN) AF: 0.854 AC: 8984 AN: 10522

Middle Eastern (MID) AF: 0.810 AC: 235 AN: 290

European-Non Finnish (NFE) AF: 0.780 AC: 53012 AN: 67946

Other (OTH) AF: 0.836 AC: 1764 AN: 2110

Alfa AF: 0.802 Hom.: 24963

Bravo AF: 0.841

Asia WGS AF: 0.952 AC: 3304 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.8
DANN	Benign	0.55
PhyloP100		-0.26
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: rs7299371; hg19: chr12-44983952;