2-121727863-T-TGA

Position:

• chr2-121727863-T-TGA

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_032390.5(NIFK):​c.741_742dupTC​(p.Gln248fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000844 in 1,606,770 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00081 (3 hom.)
• Consequence: NIFK NM_032390.5 frameshift
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.454

Genes affected

NIFK (HGNC:17838): (nucleolar protein interacting with the FHA domain of MKI67) This gene encodes a protein that interacts with the forkhead-associated domain of the Ki-67 antigen. The encoded protein may bind RNA and may play a role in mitosis and cell cycle progression. Multiple pseudogenes exist on chromosomes 5, 10, 12, 15, and 19.[provided by RefSeq, Jan 2009]

NIFK-AS1 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 2-121727863-T-TGA is Benign according to our data. Variant chr2-121727863-T-TGA is described in ClinVar as [Likely_benign]. Clinvar id is 719899.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NIFK	NM_032390.5	c.741_742dupTC	p.Gln248fs	frameshift_variant	7/7	ENST00000285814.9	NP_115766.3
NIFK-AS1	NR_037857.1	n.1147_1148dupGA		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NIFK	ENST00000285814.9	c.741_742dupTC	p.Gln248fs	frameshift_variant	7/7	1	NM_032390.5	ENSP00000285814.4

Frequencies

GnomAD3 genomes AF: 0.00114 AC: 174 AN: 152182 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00434

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00166

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000800 AC: 198 AN: 247540 Hom.: 0 AF XY: 0.000777 AC XY: 104 AN XY: 133776

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000120

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00361

Gnomad NFE exome AF: 0.000973

Gnomad OTH exome AF: 0.000495

GnomAD4 exome AF: 0.000813 AC: 1182 AN: 1454470 Hom.: 3 Cov.: 31 AF XY: 0.000836 AC XY: 605 AN XY: 723616

Gnomad4 AFR exome AF: 0.000120

Gnomad4 AMR exome AF: 0.000138

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000235

Gnomad4 FIN exome AF: 0.00313

Gnomad4 NFE exome AF: 0.000885

Gnomad4 OTH exome AF: 0.000366

GnomAD4 genome AF: 0.00114 AC: 174 AN: 152300 Hom.: 2 Cov.: 32 AF XY: 0.00122 AC XY: 91 AN XY: 74468

Gnomad4 AFR AF: 0.000216

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00434

Gnomad4 NFE AF: 0.00166

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00148 Hom.: 1

Bravo AF: 0.000525

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs561007941; hg19: chr2-122485439;