17-39605660-C-A

Variant names:

• chr17-39605660-C-A
• NM_006160.4:c.940G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006160.4(NEUROD2):​c.940G>T​(p.Asp314Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar 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: 6.12

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEUROD2	NM_006160.4	c.940G>T	p.Asp314Tyr	missense_variant	Exon 2 of 2	ENST00000302584.5	NP_006151.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEUROD2	ENST00000302584.5	c.940G>T	p.Asp314Tyr	missense_variant	Exon 2 of 2	1	NM_006160.4	ENSP00000306754.4
NEUROD2	ENST00000580874.1	n.4118G>T		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Developmental and epileptic encephalopathy, 72 Uncertain:1

Jun 30, 2022

Department Of Genetics, Sultan Qaboos University Hospital, Sultan Qaboos University

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	32
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.49	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.96	D
M_CAP	Pathogenic	0.58	D
MetaRNN	Uncertain	0.61	D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Benign	1.7	L
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Uncertain	0.63
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.99	D
Vest4		0.51
MutPred		0.26		Gain of phosphorylation at D314 (P = 0.0245);
MVP		0.73
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.83
gMVP		0.48

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-37761913; COSMIC: COSV56910772;