rs1008615740

Variant names:

• chr4-112515291-C-A
• rs1008615740
• NM_024019.4:c.185G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-112515291-C-A
• chr4-112515291-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024019.4(NEUROG2):​c.185G>T​(p.Gly62Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000756 in 1,322,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. G62E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: NEUROG2 NM_024019.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 0 publications found

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)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19061944).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024019.4. 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
	NEUROG2	NM_024019.4	MANE Select	c.185G>T	p.Gly62Val	missense	Exon 2 of 2	NP_076924.1	Q9H2A3
	NEUROG2-AS1	NR_161159.1		n.-88C>A		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEUROG2	ENST00000313341.4	TSL:1 MANE Select	c.185G>T	p.Gly62Val	missense	Exon 2 of 2	ENSP00000317333.3	Q9H2A3
	NEUROG2-AS1	ENST00000754766.1		n.162+748C>A		intron	N/A
	NEUROG2-AS1	ENST00000754767.1		n.142+310C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.56e-7 AC: 1 AN: 1322586 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 652200

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26708

American (AMR) AF: 0.00 AC: 0 AN: 22444

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22318

East Asian (EAS) AF: 0.00 AC: 0 AN: 29980

South Asian (SAS) AF: 0.00 AC: 0 AN: 70938

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5460

European-Non Finnish (NFE) AF: 9.47e-7 AC: 1 AN: 1055992

Other (OTH) AF: 0.00 AC: 0 AN: 55130

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	12
DANN	Benign	0.91
DEOGEN2	Benign	0.26	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.084	N
LIST_S2	Benign	0.49	T
M_CAP	Pathogenic	0.51	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	0.34	N
PhyloP100		-1.3
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.10
Sift	Benign	0.17	T
Sift4G	Benign	0.15	T
Polyphen		0.041	B
Vest4		0.12
MutPred		0.35		Loss of relative solvent accessibility (P = 0.0071)
MVP		0.92
MPC		0.84
ClinPred		0.075	T
GERP RS		0.24
Varity_R		0.077
gMVP		0.42
Mutation Taster		=98/2	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: rs1008615740; hg19: chr4-113436447;