rs1377002

Variant names:

• chr12-44508790-A-G
• rs1377002
• NM_001145108.2:c.*144T>C

Variant summary

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

The NM_001145108.2(NELL2):​c.*144T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 694,962 control chromosomes in the GnomAD database, including 25,710 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 0.20 (4374 hom., cov: 32)
  • Exomes 𝑓: 0.25 (21336 hom.)
• Consequence: NELL2 NM_001145108.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.499
• Publications: 7 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=-0.47).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NELL2	NM_001145108.2	c.*144T>C		3_prime_UTR_variant	Exon 20 of 20	ENST00000429094.7	NP_001138580.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NELL2	ENST00000429094.7	c.*144T>C		3_prime_UTR_variant	Exon 20 of 20	1	NM_001145108.2	ENSP00000390680.2

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30247 AN: 152012 Hom.: 4364 Cov.: 32

Gnomad AFR AF: 0.0433

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.573

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.204

GnomAD4 exome AF: 0.254 AC: 138028 AN: 542832 Hom.: 21336 Cov.: 7 AF XY: 0.262 AC XY: 74212 AN XY: 283530

African (AFR) AF: 0.0406 AC: 561 AN: 13808

American (AMR) AF: 0.423 AC: 8013 AN: 18932

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 4276 AN: 14226

East Asian (EAS) AF: 0.577 AC: 18098 AN: 31382

South Asian (SAS) AF: 0.418 AC: 19853 AN: 47442

European-Finnish (FIN) AF: 0.204 AC: 9175 AN: 45036

Middle Eastern (MID) AF: 0.219 AC: 539 AN: 2462

European-Non Finnish (NFE) AF: 0.207 AC: 70472 AN: 340972

Other (OTH) AF: 0.246 AC: 7041 AN: 28572

GnomAD4 genome AF: 0.199 AC: 30261 AN: 152130 Hom.: 4374 Cov.: 32 AF XY: 0.210 AC XY: 15624 AN XY: 74364

African (AFR) AF: 0.0432 AC: 1793 AN: 41528

American (AMR) AF: 0.364 AC: 5557 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1052 AN: 3470

East Asian (EAS) AF: 0.573 AC: 2959 AN: 5164

South Asian (SAS) AF: 0.436 AC: 2104 AN: 4822

European-Finnish (FIN) AF: 0.200 AC: 2116 AN: 10572

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 14021 AN: 67992

Other (OTH) AF: 0.206 AC: 434 AN: 2108

Alfa AF: 0.215 Hom.: 7610

Bravo AF: 0.203

Asia WGS AF: 0.460 AC: 1596 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	1.7
DANN	Benign	0.79
PhyloP100		-0.50
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: rs1377002; hg19: chr12-44902573;