chr2-219084462-C-T

Position:

• chr2-219084462-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024782.3(NHEJ1):​c.589-6256G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0597 in 152,262 control chromosomes in the GnomAD database, including 869 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 0.060 (869 hom., cov: 31)
• Consequence: NHEJ1 NM_024782.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.632

Genes affected

NHEJ1 (HGNC:25737): (non-homologous end joining factor 1) Double-strand breaks in DNA result from genotoxic stresses and are among the most damaging of DNA lesions. This gene encodes a DNA repair factor essential for the nonhomologous end-joining pathway, which preferentially mediates repair of double-stranded breaks. Mutations in this gene cause different kinds of severe combined immunodeficiency disorders. [provided by RefSeq, Jul 2008]

ENSG00000280537 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NHEJ1	NM_024782.3	c.589-6256G>A		intron_variant		ENST00000356853.10	NP_079058.1
NHEJ1	NM_001377499.1	c.589-6256G>A		intron_variant			NP_001364428.1
NHEJ1	NM_001377498.1	c.589-6256G>A		intron_variant			NP_001364427.1
NHEJ1	NR_165304.1	n.767-6256G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NHEJ1	ENST00000356853.10	c.589-6256G>A		intron_variant		1	NM_024782.3	ENSP00000349313.5
ENSG00000280537	ENST00000318673.6	n.*1711-6256G>A		intron_variant		2		ENSP00000320919.3

Frequencies

GnomAD3 genomes AF: 0.0596 AC: 9065 AN: 152144 Hom.: 867 Cov.: 31

Gnomad AFR AF: 0.0174

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.0935

Gnomad FIN AF: 0.0543

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0345

Gnomad OTH AF: 0.0664

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0597 AC: 9083 AN: 152262 Hom.: 869 Cov.: 31 AF XY: 0.0655 AC XY: 4873 AN XY: 74438

Gnomad4 AFR AF: 0.0174

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.0124

Gnomad4 EAS AF: 0.461

Gnomad4 SAS AF: 0.0939

Gnomad4 FIN AF: 0.0543

Gnomad4 NFE AF: 0.0345

Gnomad4 OTH AF: 0.0719

Alfa AF: 0.0521 Hom.: 1461

Bravo AF: 0.0694

Asia WGS AF: 0.282 AC: 977 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.7
DANN	Benign	0.58

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: rs16859517; hg19: chr2-219949184;