4-112515098-G-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The ENST00000313341.4(NEUROG2):​c.378C>A​(p.His126Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000046 in 152,228 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Consequence

NEUROG2
ENST00000313341.4 missense

Scores

8
8
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.77
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 -4 ACMG points.

BS2
High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NEUROG2NM_024019.4 linkuse as main transcriptc.378C>A p.His126Gln missense_variant 2/2 ENST00000313341.4 NP_076924.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NEUROG2ENST00000313341.4 linkuse as main transcriptc.378C>A p.His126Gln missense_variant 2/21 NM_024019.4 ENSP00000317333 P1

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152228
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000169
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
GnomAD3 exomes
AF:
0.00000797
AC:
2
AN:
250844
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135784
show subpopulations
Gnomad AFR exome
AF:
0.000124
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
34
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152228
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74360
show subpopulations
Gnomad4 AFR
AF:
0.000169
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:
0.0000227
ExAC
AF:
0.0000247
AC:
3

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 submitterclinical testingAmbry GeneticsSep 27, 2021The c.378C>A (p.H126Q) alteration is located in exon 2 (coding exon 1) of the NEUROG2 gene. This alteration results from a C to A substitution at nucleotide position 378, causing the histidine (H) at amino acid position 126 to be replaced by a glutamine (Q). 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
Pathogenic
1.0
BayesDel_addAF
Uncertain
0.054
T
BayesDel_noAF
Uncertain
0.080
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Pathogenic
0.91
D
Eigen
Uncertain
0.52
Eigen_PC
Uncertain
0.47
FATHMM_MKL
Benign
0.69
D
LIST_S2
Uncertain
0.89
D
M_CAP
Pathogenic
0.56
D
MetaRNN
Uncertain
0.59
D
MetaSVM
Pathogenic
0.94
D
MutationAssessor
Benign
1.7
L
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.88
D
PROVEAN
Pathogenic
-8.0
D
REVEL
Pathogenic
0.65
Sift
Uncertain
0.0050
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.17
MutPred
0.41
Gain of MoRF binding (P = 0.0889);
MVP
1.0
MPC
1.7
ClinPred
0.99
D
GERP RS
3.8
Varity_R
0.67
gMVP
0.92

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: rs752074567; hg19: chr4-113436254; API