NHEJ1 p.Arg151Arg

Variant names:

• chr2-219147732-C-C
• NM_024782.3:c.

Your query was ambiguous. Multiple possible variants found:

• chr2-219147733--
• chr2-219147735-T-G
• chr2-219147733-C-T
• chr2-219147733-CCT-ACG
• chr2-219147733-CCT-GCG
• chr2-219147733-CCT-TCG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024782.3(NHEJ1):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NHEJ1 NM_024782.3 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.331
• Publications: 0 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: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

ENSG00000280537 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024782.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NHEJ1	NM_024782.3	MANE Select	c.		exon_region	Exon 4 of 8	NP_079058.1	Q9H9Q4-1
	NHEJ1	NM_001377499.1		c.		exon_region	Exon 4 of 8	NP_001364428.1	H7C0G7
	NHEJ1	NM_001377498.1		c.		exon_region	Exon 4 of 8	NP_001364427.1	Q9H9Q4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NHEJ1	ENST00000356853.10	TSL:1 MANE Select	c.		exon_region	Exon 4 of 8	ENSP00000349313.5	Q9H9Q4-1
	ENSG00000280537	ENST00000318673.6	TSL:2	n.		exon_region	Exon 13 of 17	ENSP00000320919.3	F8W735
	ENSG00000280537	ENST00000318673.6	TSL:2	n.		3_prime_UTR	Exon 13 of 17	ENSP00000320919.3	F8W735

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.33

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-220012454;