2-219069626-G-T

Variant names:

• chr2-219069626-G-T
• rs1052483
• NM_024782.3:c.*6755C>A

Variant summary

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

The NM_024782.3(NHEJ1):​c.*6755C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,240 control chromosomes in the GnomAD database, including 1,349 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 0.13 (1349 hom., cov: 32)
  • Exomes 𝑓: 0.11 (0 hom.)
• Consequence: NHEJ1 NM_024782.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.655
• Publications: 23 publications found

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]

NHEJ1 Gene-Disease associations (from GenCC):

• Cernunnos-XLF deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

ENSG00000286606 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NHEJ1	NM_024782.3	c.*6755C>A		3_prime_UTR_variant	Exon 8 of 8	ENST00000356853.10	NP_079058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NHEJ1	ENST00000356853.10	c.*6755C>A		3_prime_UTR_variant	Exon 8 of 8	1	NM_024782.3	ENSP00000349313.5

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19161 AN: 152102 Hom.: 1342 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.0617

Gnomad FIN AF: 0.0825

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0977

Gnomad OTH AF: 0.127

GnomAD4 exome AF: 0.111 AC: 2 AN: 18 Hom.: 0 Cov.: 0 AF XY: 0.0833 AC XY: 1 AN XY: 12

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.167 AC: 1 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 10

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.126 AC: 19196 AN: 152222 Hom.: 1349 Cov.: 32 AF XY: 0.124 AC XY: 9231 AN XY: 74442

African (AFR) AF: 0.199 AC: 8259 AN: 41498

American (AMR) AF: 0.105 AC: 1601 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 357 AN: 3468

East Asian (EAS) AF: 0.145 AC: 754 AN: 5190

South Asian (SAS) AF: 0.0619 AC: 299 AN: 4828

European-Finnish (FIN) AF: 0.0825 AC: 875 AN: 10600

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0977 AC: 6648 AN: 68026

Other (OTH) AF: 0.128 AC: 270 AN: 2116

Alfa AF: 0.108 Hom.: 3196

Bravo AF: 0.134

Asia WGS AF: 0.129 AC: 448 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.9
DANN	Benign	0.78
PhyloP100		-0.66

Splicing

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

Other links and lift over

dbSNP: rs1052483; hg19: chr2-219934348;