Genetic Variant NM_024782.3:c.825+20delC (chr2-219077225-AG-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP6_Moderate

The NM_024782.3(NHEJ1):c.825+20delC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000703 in 1,422,422 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000070 ( 0 hom. )

Consequence

NHEJ1
NM_024782.3 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.484

Publications

0 publications found

Variant links:

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)

NHEJ1 links:

ENSG00000280537 (HGNC:):

ENSG00000280537 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 2-219077225-AG-A is Benign according to our data. Variant chr2-219077225-AG-A is described in ClinVar as [Likely_benign]. Clinvar id is 1907308.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
NHEJ1	NM_024782.3 link	c.825+20delC	intron_variant	Intron 7 of 7	ENST00000356853.10	NP_079058.1	Q9H9Q4-1
NHEJ1	NM_001377499.1 link	c.840+20delC	intron_variant	Intron 7 of 7		NP_001364428.1
NHEJ1	NM_001377498.1 link	c.825+20delC	intron_variant	Intron 7 of 7		NP_001364427.1
NHEJ1	NR_165304.1 link	n.1003+20delC	intron_variant	Intron 8 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NHEJ1	ENST00000356853.10 link	c.825+20delC		intron_variant	Intron 7 of 7	1	NM_024782.3	ENSP00000349313.5		Q9H9Q4-1
ENSG00000280537	ENST00000318673.6 link	n.*1947+20delC		intron_variant	Intron 16 of 16	2		ENSP00000320919.3		F8W735

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251162

AF XY:

0.00000737

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000703

AC:

AN:

1422422

Hom.:

Cov.:

AF XY:

0.00000563

AC XY:

AN XY:

710292

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32620

American (AMR)

AF:

0.00

AC:

AN:

44658

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25908

East Asian (EAS)

AF:

0.00

AC:

AN:

39486

South Asian (SAS)

AF:

0.00

AC:

AN:

85412

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5520

European-Non Finnish (NFE)

AF:

0.00000929

AC:

AN:

1076380

Other (OTH)

AF:

0.00

AC:

AN:

59042

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.560

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Cernunnos-XLF deficiency

Benign:1

Aug 31, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.48

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

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NM_024782.3:c.825+20delC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over