chr12-44508790-A-G

Position:

• chr12-44508790-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
NELL2	NM_001145108.2	c.*144T>C		3_prime_UTR_variant	20/20	ENST00000429094.7	NP_001138580.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NELL2	ENST00000429094.7	c.*144T>C		3_prime_UTR_variant	20/20	1	NM_001145108.2	ENSP00000390680	P1

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

Gnomad4 AFR exome AF: 0.0406

Gnomad4 AMR exome AF: 0.423

Gnomad4 ASJ exome AF: 0.301

Gnomad4 EAS exome AF: 0.577

Gnomad4 SAS exome AF: 0.418

Gnomad4 FIN exome AF: 0.204

Gnomad4 NFE exome AF: 0.207

Gnomad4 OTH exome AF: 0.246

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

Gnomad4 AFR AF: 0.0432

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.303

Gnomad4 EAS AF: 0.573

Gnomad4 SAS AF: 0.436

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.206

Alfa AF: 0.216 Hom.: 5334

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

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: rs1377002; hg19: chr12-44902573;