2-177230805-G-C

Position:

• chr2-177230805-G-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_006164.5(NFE2L2):​c.1798C>G​(p.Pro600Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,434,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: NFE2L2 NM_006164.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.20

Genes affected

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04245767).
• BP6: Variant 2-177230805-G-C is Benign according to our data. Variant chr2-177230805-G-C is described in ClinVar as [Benign]. Clinvar id is 1983897.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFE2L2	NM_006164.5	c.1798C>G	p.Pro600Ala	missense_variant	5/5	ENST00000397062.8	NP_006155.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFE2L2	ENST00000397062.8	c.1798C>G	p.Pro600Ala	missense_variant	5/5	1	NM_006164.5	ENSP00000380252.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.97e-7 AC: 1 AN: 1434810 Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1 AN XY: 712626

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.06e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

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

Labcorp Genetics (formerly Invitae), Labcorp

Nov 27, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	15
DANN	Benign	0.80
DEOGEN2	Benign	0.074	.;T;.;.
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.22
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.77	.;T;T;T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.042	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	.;N;.;.
MutationTaster	Benign	0.89	N;N;N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.56	N;N;N;.
REVEL	Benign	0.045
Sift	Benign	0.47	T;T;T;.
Sift4G	Benign	0.67	T;T;T;T
Polyphen		0.0010	.;B;.;.
Vest4		0.11
MutPred		0.17		.;Gain of MoRF binding (P = 0.0328);.;.;
MVP		0.23
MPC		0.14
ClinPred		0.10	T
GERP RS		4.1
Varity_R		0.031
gMVP		0.22

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: rs1689515041; hg19: chr2-178095533;