Variant chr6-108176649-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_003269.5(NR2E1):c.406C>G(p.Gln136Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

NR2E1
NM_003269.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.46

Variant links:

Genes affected

NR2E1 (HGNC:7973): (nuclear receptor subfamily 2 group E member 1) The protein encoded by this gene is an orphan receptor involved in retinal development. The encoded protein also regulates adult neural stem cell proliferation and may be involved in control of aggressive behavior. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2015]

NR2E1 links:

NR2E1 (HGNC:):

NR2E1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.41138104).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR2E1	NM_003269.5 linkuse as main transcript	c.406C>G	p.Gln136Glu	missense_variant	4/9	ENST00000368986.9	NP_003260.1	Q9Y466-1B6ZGT9
NR2E1	NM_001286102.1 linkuse as main transcript	c.517C>G	p.Gln173Glu	missense_variant	4/9		NP_001273031.1	Q9Y466-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NR2E1	ENST00000368986.9 linkuse as main transcript	c.406C>G	p.Gln136Glu	missense_variant	4/9	1	NM_003269.5	ENSP00000357982.5	Q9Y466-1
NR2E1	ENST00000368983.3 linkuse as main transcript	c.517C>G	p.Gln173Glu	missense_variant	4/9	2		ENSP00000357979.3	Q9Y466-2
NR2E1	ENST00000484978.1 linkuse as main transcript	n.369C>G		non_coding_transcript_exon_variant	2/3	5
NR2E1	ENST00000426403.1 linkuse as main transcript	c.*23C>G		downstream_gene_variant		4		ENSP00000416908.1	A6PVF6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1455596

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724094

show subpopulations

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 27, 2022

The c.406C>G (p.Q136E) alteration is located in exon 4 (coding exon 4) of the NR2E1 gene. This alteration results from a C to G substitution at nucleotide position 406, causing the glutamine (Q) at amino acid position 136 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.00011

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Benign

0.73

DEOGEN2

Benign

0.15

T;.

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.019

MetaRNN

Benign

0.41

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;.

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.34

N;N

REVEL

Benign

0.13

Sift

Benign

0.99

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.63

P;.

Vest4

0.69

MutPred

0.28

Gain of disorder (P = 0.0681);.;

MVP

0.51

MPC

0.93

ClinPred

0.68

GERP RS

5.8

Varity_R

0.24

gMVP

0.71

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over