17-39605770-A-T

Variant names:

• chr17-39605770-A-T
• NM_006160.4:c.830T>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006160.4(NEUROD2):​c.830T>A​(p.Leu277Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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: 6.66
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.82

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.830T>A	p.Leu277Gln	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.830T>A	p.Leu277Gln	missense	Exon 2 of 2	ENSP00000306754.4	Q15784
	NEUROD2	ENST00000907630.1		c.830T>A	p.Leu277Gln	missense	Exon 2 of 2	ENSP00000577689.1
	NEUROD2	ENST00000907631.1		c.830T>A	p.Leu277Gln	missense	Exon 2 of 2	ENSP00000577690.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	Benign	0.20
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	30
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.54	T
M_CAP	Pathogenic	0.65	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.44	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		6.7
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.36
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.087	T
Polyphen		0.99	D
Vest4		0.59
MutPred		0.58		Gain of catalytic residue at L277 (P = 0.0012)
MVP		0.78
ClinPred		0.94	D
GERP RS		5.7
Varity_R		0.47
gMVP		0.57

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

hg19: chr17-37762023;