2-219076956-T-C

Position:

• chr2-219076956-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_024782.3(NHEJ1):​c.825+290A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0323 in 152,266 control chromosomes in the GnomAD database, including 130 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.032 (130 hom., cov: 32)
• Consequence: NHEJ1 NM_024782.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.843

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 2-219076956-T-C is Benign according to our data. Variant chr2-219076956-T-C is described in ClinVar as [Benign]. Clinvar id is 1237087.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0323 (4921/152266) while in subpopulation NFE AF= 0.046 (3128/68028). AF 95% confidence interval is 0.0446. There are 130 homozygotes in gnomad4. There are 2524 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 130 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NHEJ1	NM_024782.3	c.825+290A>G		intron_variant		ENST00000356853.10	NP_079058.1
NHEJ1	NM_001377498.1	c.825+290A>G		intron_variant			NP_001364427.1
NHEJ1	NM_001377499.1	c.840+290A>G		intron_variant			NP_001364428.1
NHEJ1	NR_165304.1	n.1003+290A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NHEJ1	ENST00000356853.10	c.825+290A>G		intron_variant		1	NM_024782.3	ENSP00000349313	P4

Frequencies

GnomAD3 genomes AF: 0.0323 AC: 4921 AN: 152148 Hom.: 130 Cov.: 32

Gnomad AFR AF: 0.00883

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.0300

Gnomad ASJ AF: 0.0159

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.00973

Gnomad FIN AF: 0.0725

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0460

Gnomad OTH AF: 0.0254

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0323 AC: 4921 AN: 152266 Hom.: 130 Cov.: 32 AF XY: 0.0339 AC XY: 2524 AN XY: 74464

Gnomad4 AFR AF: 0.00881

Gnomad4 AMR AF: 0.0300

Gnomad4 ASJ AF: 0.0159

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.00995

Gnomad4 FIN AF: 0.0725

Gnomad4 NFE AF: 0.0460

Gnomad4 OTH AF: 0.0251

Alfa AF: 0.0393 Hom.: 15

Bravo AF: 0.0279

Asia WGS AF: 0.00606 AC: 22 AN: 3478

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

Jun 17, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.8
DANN	Benign	0.34

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: rs34828046; hg19: chr2-219941678;