2-177329052-T-C

Variant names:

• chr2-177329052-T-C
• rs10930785
• ENST00000397057.6:n.549+2520A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000397057.6(ENSG00000213963):​n.549+2520A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.82 in 151,676 control chromosomes in the GnomAD database, including 51,206 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.82 (51206 hom., cov: 31)
• Consequence: ENSG00000213963 ENST00000397057.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.51
• Publications: 5 publications found

Genes affected

ENSG00000213963 (HGNC:):

NFE2L2 (HGNC:7782): (NFE2 like bZIP transcription factor 2) This gene encodes a transcription factor which is a member of a small family of basic leucine zipper (bZIP) proteins. The encoded transcription factor regulates genes which contain antioxidant response elements (ARE) in their promoters; many of these genes encode proteins involved in response to injury and inflammation which includes the production of free radicals. Multiple transcript variants encoding different isoforms have been characterized for this gene. [provided by RefSeq, Sep 2015]

NFE2L2 Gene-Disease associations (from GenCC):

• immunodeficiency, developmental delay, and hypohomocysteinemia

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Illumina, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC100130691	NR_026966.1	n.553+2520A>G		intron_variant	Intron 5 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000213963	ENST00000397057.6	n.549+2520A>G		intron_variant	Intron 5 of 8	1
ENSG00000213963	ENST00000430416.6	n.474+5341A>G		intron_variant	Intron 5 of 9	1
ENSG00000213963	ENST00000447413.2	n.458+3090A>G		intron_variant	Intron 4 of 5	1

Frequencies

GnomAD3 genomes AF: 0.820 AC: 124304 AN: 151558 Hom.: 51150 Cov.: 31

Gnomad AFR AF: 0.801

Gnomad AMI AF: 0.932

Gnomad AMR AF: 0.862

Gnomad ASJ AF: 0.793

Gnomad EAS AF: 0.980

Gnomad SAS AF: 0.895

Gnomad FIN AF: 0.839

Gnomad MID AF: 0.783

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.820

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

GnomAD4 genome AF: 0.820 AC: 124415 AN: 151676 Hom.: 51206 Cov.: 31 AF XY: 0.824 AC XY: 61127 AN XY: 74158

African (AFR) AF: 0.801 AC: 33081 AN: 41276

American (AMR) AF: 0.862 AC: 13155 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.793 AC: 2755 AN: 3472

East Asian (EAS) AF: 0.980 AC: 5055 AN: 5156

South Asian (SAS) AF: 0.895 AC: 4314 AN: 4818

European-Finnish (FIN) AF: 0.839 AC: 8831 AN: 10522

Middle Eastern (MID) AF: 0.774 AC: 226 AN: 292

European-Non Finnish (NFE) AF: 0.802 AC: 54416 AN: 67860

Other (OTH) AF: 0.823 AC: 1736 AN: 2110

Alfa AF: 0.807 Hom.: 207556

Bravo AF: 0.820

Asia WGS AF: 0.926 AC: 3219 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.27
DANN	Benign	0.21
PhyloP100		-3.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs10930785; hg19: chr2-178193780; COSMIC: COSV67957786;