2-219076557-C-CT

Position:

• chr2-219076557-C-CT

Variant summary

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

The ENST00000356853.10(NHEJ1):​c.826-103_826-102insA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0512 in 445,678 control chromosomes in the GnomAD database, including 88 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.031 (87 hom., cov: 28)
  • Exomes 𝑓: 0.059 (1 hom.)
• Consequence: NHEJ1 ENST00000356853.10 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.188

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-C-CT is Benign according to our data. Variant chr2-219076557-C-CT is described in ClinVar as [Benign]. Clinvar id is 1234916.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NHEJ1	NM_024782.3	c.826-103_826-102insA		intron_variant		ENST00000356853.10	NP_079058.1
NHEJ1	NM_001377498.1	c.826-103_826-102insA		intron_variant			NP_001364427.1
NHEJ1	NM_001377499.1	c.841-103_841-102insA		intron_variant			NP_001364428.1
NHEJ1	NR_165304.1	n.1004-103_1004-102insA		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NHEJ1	ENST00000356853.10	c.826-103_826-102insA		intron_variant		1	NM_024782.3	ENSP00000349313	P4

Frequencies

GnomAD3 genomes AF: 0.0310 AC: 3788 AN: 122378 Hom.: 87 Cov.: 28

Gnomad AFR AF: 0.0627

Gnomad AMI AF: 0.0443

Gnomad AMR AF: 0.0179

Gnomad ASJ AF: 0.0256

Gnomad EAS AF: 0.00905

Gnomad SAS AF: 0.0115

Gnomad FIN AF: 0.00441

Gnomad MID AF: 0.0119

Gnomad NFE AF: 0.0219

Gnomad OTH AF: 0.0267

GnomAD4 exome AF: 0.0588 AC: 19016 AN: 323324 Hom.: 1 AF XY: 0.0585 AC XY: 10365 AN XY: 177308

Gnomad4 AFR exome AF: 0.0739

Gnomad4 AMR exome AF: 0.0626

Gnomad4 ASJ exome AF: 0.0551

Gnomad4 EAS exome AF: 0.0530

Gnomad4 SAS exome AF: 0.0747

Gnomad4 FIN exome AF: 0.0489

Gnomad4 NFE exome AF: 0.0563

Gnomad4 OTH exome AF: 0.0563

GnomAD4 genome AF: 0.0310 AC: 3790 AN: 122354 Hom.: 87 Cov.: 28 AF XY: 0.0303 AC XY: 1777 AN XY: 58578

Gnomad4 AFR AF: 0.0627

Gnomad4 AMR AF: 0.0179

Gnomad4 ASJ AF: 0.0256

Gnomad4 EAS AF: 0.00909

Gnomad4 SAS AF: 0.0116

Gnomad4 FIN AF: 0.00441

Gnomad4 NFE AF: 0.0219

Gnomad4 OTH AF: 0.0265

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

Oct 28, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs778354452; hg19: chr2-219941279;