rs1689515041

Variant names:

• chr2-177230805-G-A
• rs1689515041
• NM_006164.5:c.1798C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-177230805-G-A
• chr2-177230805-G-C
• chr2-177230805-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006164.5(NFE2L2):​c.1798C>T​(p.Pro600Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P600A) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NFE2L2 NM_006164.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.20
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• immunodeficiency, developmental delay, and hypohomocysteinemia

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046081632).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006164.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFE2L2	NM_006164.5	MANE Select	c.1798C>T	p.Pro600Ser	missense	Exon 5 of 5	NP_006155.2
	NFE2L2	NM_001145412.3		c.1750C>T	p.Pro584Ser	missense	Exon 5 of 5	NP_001138884.1	Q16236-2
	NFE2L2	NM_001313900.1		c.1750C>T	p.Pro584Ser	missense	Exon 5 of 5	NP_001300829.1	Q16236-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFE2L2	ENST00000397062.8	TSL:1 MANE Select	c.1798C>T	p.Pro600Ser	missense	Exon 5 of 5	ENSP00000380252.3	Q16236-1
	NFE2L2	ENST00000397063.9	TSL:1	c.1750C>T	p.Pro584Ser	missense	Exon 5 of 5	ENSP00000380253.4	Q16236-2
	NFE2L2	ENST00000421929.6	TSL:1	c.1750C>T	p.Pro584Ser	missense	Exon 5 of 5	ENSP00000412191.2	Q16236-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	16
DANN	Benign	0.95
DEOGEN2	Benign	0.075	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.49	N
PhyloP100		2.2
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.49	N
REVEL	Benign	0.049
Sift	Benign	0.33	T
Sift4G	Benign	0.55	T
Polyphen		0.0080	B
Vest4		0.070
MutPred		0.16		Gain of phosphorylation at P600 (P = 0.0191)
MVP		0.24
MPC		0.15
ClinPred		0.21	T
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.035
gMVP		0.23
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs1689515041; hg19: chr2-178095533;