rs1736402377

Variant names:

• chr4-112515147-T-C
• rs1736402377
• NM_024019.4:c.329A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Moderate BS2

The NM_024019.4(NEUROG2):​c.329A>G​(p.Lys110Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,424 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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: 0.0000034 (0 hom.)
• Consequence: NEUROG2 NM_024019.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.05
• 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18449995).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

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.329A>G	p.Lys110Arg	missense	Exon 2 of 2	NP_076924.1	Q9H2A3
	NEUROG2-AS1	NR_161159.1		n.-232T>C		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.329A>G	p.Lys110Arg	missense	Exon 2 of 2	ENSP00000317333.3	Q9H2A3
	NEUROG2-AS1	ENST00000754766.1		n.162+604T>C		intron	N/A
	NEUROG2-AS1	ENST00000754767.1		n.142+166T>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461424 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2 AN XY: 727056

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.0000224 AC: 1 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53144

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111880

Other (OTH) AF: 0.0000331 AC: 2 AN: 60376

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.0050	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.34	T
Eigen	Benign	-0.078
Eigen_PC	Benign	-0.029
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.66	T
M_CAP	Pathogenic	0.30	D
MetaRNN	Benign	0.18	T
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Benign	0.81	L
PhyloP100		3.0
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.96	N
REVEL	Uncertain	0.41
Sift	Benign	0.30	T
Sift4G	Benign	0.54	T
Polyphen		0.24	B
Vest4		0.078
MutPred		0.22		Loss of glycosylation at K110 (P = 0.0471)
MVP		0.86
MPC		1.5
ClinPred		0.70	D
GERP RS		3.7
Varity_R		0.19
gMVP		0.80
Mutation Taster		=93/7	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: rs1736402377; hg19: chr4-113436303;