17-39605480-C-T

Variant names:

• chr17-39605480-C-T
• rs766977904
• NM_006160.4:c.1120G>A

Variant summary

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

The NM_006160.4(NEUROD2):​c.1120G>A​(p.Glu374Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E374Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NEUROD2 NM_006160.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.81
• Publications: 0 publications found

Genes affected

NEUROD2 (HGNC:7763): (neuronal differentiation 2) This gene encodes a member of the neuroD family of neurogenic basic helix-loop-helix (bHLH) proteins. Expression of this gene can induce transcription from neuron-specific promoters, such as the GAP-43 promoter, which contain a specific DNA sequence known as an E-box. The product of the human gene can induce neurogenic differentiation in non-neuronal cells in Xenopus embryos, and is thought to play a role in the determination and maintenance of neuronal cell fates. [provided by RefSeq, Jul 2008]

NEUROD2 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 72

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006160.4. 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
	NEUROD2	NM_006160.4	MANE Select	c.1120G>A	p.Glu374Lys	missense	Exon 2 of 2	NP_006151.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEUROD2	ENST00000302584.5	TSL:1 MANE Select	c.1120G>A	p.Glu374Lys	missense	Exon 2 of 2	ENSP00000306754.4	Q15784
	NEUROD2	ENST00000907630.1		c.1120G>A	p.Glu374Lys	missense	Exon 2 of 2	ENSP00000577689.1
	NEUROD2	ENST00000907631.1		c.1120G>A	p.Glu374Lys	missense	Exon 2 of 2	ENSP00000577690.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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 provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.92	D
M_CAP	Pathogenic	0.34	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Uncertain	0.71	D
MutationAssessor	Benign	2.0	M
PhyloP100		4.8
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.59
Sift	Benign	0.047	D
Sift4G	Benign	0.12	T
Polyphen		0.99	D
Vest4		0.39
MutPred		0.42		Gain of ubiquitination at E374 (P = 0.0155)
MVP		0.67
ClinPred		0.89	D
GERP RS		5.1
Varity_R		0.37
gMVP		0.28

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: rs766977904; hg19: chr17-37761733;