NM_024782.3:c.806C>G

Variant names:

• chr2-219077265-G-C
• NM_024782.3:c.806C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024782.3(NHEJ1):​c.806C>G​(p.Ala269Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NHEJ1 NM_024782.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.26

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.023201108).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NHEJ1	NM_024782.3	c.806C>G	p.Ala269Gly	missense_variant	Exon 7 of 8	ENST00000356853.10	NP_079058.1
NHEJ1	NM_001377499.1	c.821C>G	p.Ala274Gly	missense_variant	Exon 7 of 8		NP_001364428.1
NHEJ1	NM_001377498.1	c.806C>G	p.Ala269Gly	missense_variant	Exon 7 of 8		NP_001364427.1
NHEJ1	NR_165304.1	n.984C>G		non_coding_transcript_exon_variant	Exon 8 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NHEJ1	ENST00000356853.10	c.806C>G	p.Ala269Gly	missense_variant	Exon 7 of 8	1	NM_024782.3	ENSP00000349313.5
ENSG00000280537	ENST00000318673.6	n.*1928C>G		non_coding_transcript_exon_variant	Exon 16 of 17	2		ENSP00000320919.3
ENSG00000280537	ENST00000318673.6	n.*1928C>G		3_prime_UTR_variant	Exon 16 of 17	2		ENSP00000320919.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460830 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726792

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.0020
DANN	Benign	0.45
DEOGEN2	Benign	0.029	.;T;.
Eigen	Benign	-2.4
Eigen_PC	Benign	-2.5
FATHMM_MKL	Benign	0.0083	N
LIST_S2	Benign	0.41	T;T;T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.023	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	N;N;.
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.81	N;N;N
REVEL	Benign	0.065
Sift	Benign	0.52	T;T;T
Sift4G	Benign	0.44	T;T;T
Polyphen		0.0	.;B;.
Vest4		0.052
MutPred		0.071		Gain of glycosylation at S268 (P = 0.0443);Gain of glycosylation at S268 (P = 0.0443);.;
MVP		0.35
MPC		0.048
ClinPred		0.011	T
GERP RS		-10
Varity_R		0.017
gMVP		0.11

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-219941987;