2-219076557-CTTTTTTTTTT-C

Position:

• chr2-219076557-CTTTTTTTTTT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_024782.3(NHEJ1):​c.826-112_826-103del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0073 in 457,698 control chromosomes in the GnomAD database, including 87 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (79 hom., cov: 28)
  • Exomes 𝑓: 0.0028 (8 hom.)
• Consequence: NHEJ1 NM_024782.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.16

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-219076557-CTTTTTTTTTT-C is Benign according to our data. Variant chr2-219076557-CTTTTTTTTTT-C is described in ClinVar as [Benign]. Clinvar id is 1225248.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NHEJ1	NM_024782.3	c.826-112_826-103del		intron_variant		ENST00000356853.10	NP_079058.1
NHEJ1	NM_001377498.1	c.826-112_826-103del		intron_variant			NP_001364427.1
NHEJ1	NM_001377499.1	c.841-112_841-103del		intron_variant			NP_001364428.1
NHEJ1	NR_165304.1	n.1004-112_1004-103del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NHEJ1	ENST00000356853.10	c.826-112_826-103del		intron_variant		1	NM_024782.3	ENSP00000349313	P4

Frequencies

GnomAD3 genomes AF: 0.0196 AC: 2398 AN: 122550 Hom.: 79 Cov.: 28

Gnomad AFR AF: 0.0693

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00838

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000256

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000172

Gnomad OTH AF: 0.0157

GnomAD4 exome AF: 0.00282 AC: 946 AN: 335172 Hom.: 8 AF XY: 0.00224 AC XY: 413 AN XY: 183988

Gnomad4 AFR exome AF: 0.0793

Gnomad4 AMR exome AF: 0.00623

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000196

Gnomad4 OTH exome AF: 0.00534

GnomAD4 genome AF: 0.0196 AC: 2397 AN: 122526 Hom.: 79 Cov.: 28 AF XY: 0.0190 AC XY: 1116 AN XY: 58650

Gnomad4 AFR AF: 0.0692

Gnomad4 AMR AF: 0.00838

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000257

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000172

Gnomad4 OTH AF: 0.0156

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 13, 2021

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs778354452; hg19: chr2-219941279;