4-112514946-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_024019.4(NEUROG2):​c.530G>A​(p.Gly177Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,611,300 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

NEUROG2
NM_024019.4 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.171
Variant links:
Genes affected
NEUROG2 (HGNC:13805): (neurogenin 2) This gene encodes a neural-specific basic helix-loop-helix (bHLH) transcription factor that can specify a neuronal fate on ectodermal cells and is expressed in neural progenitor cells within the developing central and peripheral nervous systems. The protein product of this gene also plays a role in the differentiation and survival of midbrain dopaminergic neurons. [provided by RefSeq, Apr 2012]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.14269969).
BS2
High AC in GnomAdExome4 at 26 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NEUROG2NM_024019.4 linkc.530G>A p.Gly177Asp missense_variant Exon 2 of 2 ENST00000313341.4 NP_076924.1 Q9H2A3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NEUROG2ENST00000313341.4 linkc.530G>A p.Gly177Asp missense_variant Exon 2 of 2 1 NM_024019.4 ENSP00000317333.3 Q9H2A3

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
151910
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000414
AC:
1
AN:
241748
Hom.:
0
AF XY:
0.00000757
AC XY:
1
AN XY:
132128
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000921
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000178
AC:
26
AN:
1459390
Hom.:
0
Cov.:
33
AF XY:
0.0000193
AC XY:
14
AN XY:
725878
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:
0.0000234
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
151910
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74162
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.00000827
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 23, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.530G>A (p.G177D) alteration is located in exon 2 (coding exon 1) of the NEUROG2 gene. This alteration results from a G to A substitution at nucleotide position 530, causing the glycine (G) at amino acid position 177 to be replaced by an aspartic acid (D). 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
0.16
BayesDel_addAF
Uncertain
0.072
D
BayesDel_noAF
Benign
-0.13
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.38
T
Eigen
Benign
-0.80
Eigen_PC
Benign
-0.78
FATHMM_MKL
Benign
0.098
N
LIST_S2
Benign
0.39
T
M_CAP
Benign
0.051
D
MetaRNN
Benign
0.14
T
MetaSVM
Benign
-0.43
T
MutationAssessor
Benign
0.0
N
PrimateAI
Pathogenic
0.83
D
PROVEAN
Benign
-0.20
N
REVEL
Benign
0.27
Sift
Benign
0.047
D
Sift4G
Uncertain
0.020
D
Polyphen
0.0030
B
Vest4
0.30
MutPred
0.36
Gain of solvent accessibility (P = 0.1014);
MVP
0.90
MPC
1.2
ClinPred
0.076
T
GERP RS
2.6
Varity_R
0.094
gMVP
0.79

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs752072801; hg19: chr4-113436102; API