chr4-112515318-C-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_024019.4(NEUROG2):​c.158G>C​(p.Arg53Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000017 in 1,415,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

NEUROG2
NM_024019.4 missense

Scores

2
17

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.38
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]
NEUROG2-AS1 (HGNC:40656): (NEUROG2 and ZGRF1 antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.23159039).
BP6
Variant 4-112515318-C-G is Benign according to our data. Variant chr4-112515318-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3195516.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAdExome4 at 23 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NEUROG2NM_024019.4 linkc.158G>C p.Arg53Pro missense_variant Exon 2 of 2 ENST00000313341.4 NP_076924.1 Q9H2A3
NEUROG2-AS1NR_161159.1 linkn.-61C>G upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NEUROG2ENST00000313341.4 linkc.158G>C p.Arg53Pro missense_variant Exon 2 of 2 1 NM_024019.4 ENSP00000317333.3 Q9H2A3
NEUROG2-AS1ENST00000504009.1 linkn.-113C>G upstream_gene_variant 3
NEUROG2-AS1ENST00000506057.1 linkn.-67C>G upstream_gene_variant 3

Frequencies

GnomAD3 genomes
AF:
0.00000659
AC:
1
AN:
151826
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000242
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000182
AC:
23
AN:
1263788
Hom.:
0
Cov.:
33
AF XY:
0.0000161
AC XY:
10
AN XY:
620776
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:
0.0000224
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000659
AC:
1
AN:
151826
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74166
show subpopulations
Gnomad4 AFR
AF:
0.0000242
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Feb 27, 2024
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.068
BayesDel_addAF
Benign
-0.077
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
5.3
DANN
Benign
0.29
DEOGEN2
Benign
0.23
T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.13
N
LIST_S2
Benign
0.33
T
M_CAP
Pathogenic
0.68
D
MetaRNN
Benign
0.23
T
MetaSVM
Benign
-0.54
T
MutationAssessor
Benign
0.34
N
PrimateAI
Pathogenic
0.86
D
PROVEAN
Benign
0.79
N
REVEL
Benign
0.25
Sift
Benign
0.25
T
Sift4G
Benign
0.29
T
Polyphen
0.92
P
Vest4
0.056
MutPred
0.25
Gain of loop (P = 0.0097);
MVP
0.63
MPC
0.96
ClinPred
0.95
D
GERP RS
0.57
Varity_R
0.096
gMVP
0.41

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: rs762531271; hg19: chr4-113436474; API