2-231456145-G-GA

Position:

• chr2-231456145-G-GA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005381.3(NCL):​c.1706-10dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 1,582,116 control chromosomes in the GnomAD database, including 55,823 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (6896 hom., cov: 0)
  • Exomes 𝑓: 0.27 (48927 hom.)
• Consequence: NCL NM_005381.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.72

Genes affected

NCL (HGNC:7667): (nucleolin) Nucleolin (NCL), a eukaryotic nucleolar phosphoprotein, is involved in the synthesis and maturation of ribosomes. It is located mainly in dense fibrillar regions of the nucleolus. Human NCL gene consists of 14 exons with 13 introns and spans approximately 11kb. The intron 11 of the NCL gene encodes a small nucleolar RNA, termed U20. [provided by RefSeq, Jul 2008]

NCL (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-231456145-G-GA is Benign according to our data. Variant chr2-231456145-G-GA is described in ClinVar as [Benign]. Clinvar id is 1239082.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCL	NM_005381.3	c.1706-10dupT		intron_variant		ENST00000322723.9	NP_005372.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCL	ENST00000322723.9	c.1706-10dupT		intron_variant		2	NM_005381.3	ENSP00000318195.4

Frequencies

GnomAD3 genomes AF: 0.297 AC: 44688 AN: 150716 Hom.: 6896 Cov.: 0

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.0671

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.315

GnomAD3 exomes AF: 0.268 AC: 58535 AN: 218190 Hom.: 6329 AF XY: 0.269 AC XY: 31793 AN XY: 118092

Gnomad AFR exome AF: 0.359

Gnomad AMR exome AF: 0.227

Gnomad ASJ exome AF: 0.340

Gnomad EAS exome AF: 0.0751

Gnomad SAS exome AF: 0.212

Gnomad FIN exome AF: 0.246

Gnomad NFE exome AF: 0.306

Gnomad OTH exome AF: 0.301

GnomAD4 exome AF: 0.272 AC: 388980 AN: 1431282 Hom.: 48927 Cov.: 33 AF XY: 0.271 AC XY: 192899 AN XY: 711892

Gnomad4 AFR exome AF: 0.352

Gnomad4 AMR exome AF: 0.217

Gnomad4 ASJ exome AF: 0.330

Gnomad4 EAS exome AF: 0.0767

Gnomad4 SAS exome AF: 0.193

Gnomad4 FIN exome AF: 0.241

Gnomad4 NFE exome AF: 0.284

Gnomad4 OTH exome AF: 0.269

GnomAD4 genome AF: 0.296 AC: 44702 AN: 150834 Hom.: 6896 Cov.: 0 AF XY: 0.290 AC XY: 21366 AN XY: 73560

Gnomad4 AFR AF: 0.357

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.0673

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.238

Gnomad4 NFE AF: 0.300

Gnomad4 OTH AF: 0.314

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs150234462; hg19: chr2-232320856;