chr17-39605644-T-G

Variant names:

• chr17-39605644-T-G
• rs778638603
• NM_006160.4:c.956A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006160.4(NEUROD2):​c.956A>C​(p.His319Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. H319R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NEUROD2 NM_006160.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.10
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38862985).

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.956A>C	p.His319Pro	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.956A>C	p.His319Pro	missense	Exon 2 of 2	ENSP00000306754.4	Q15784
	NEUROD2	ENST00000907630.1		c.956A>C	p.His319Pro	missense	Exon 2 of 2	ENSP00000577689.1
	NEUROD2	ENST00000907631.1		c.956A>C	p.His319Pro	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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	23
DANN	Benign	0.89
DEOGEN2	Uncertain	0.42	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.055
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.35	T
M_CAP	Pathogenic	0.70	D
MetaRNN	Benign	0.39	T
MetaSVM	Uncertain	0.49	D
MutationAssessor	Benign	1.1	L
PhyloP100		2.1
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.45
Sift	Benign	0.14	T
Sift4G	Benign	0.085	T
Polyphen		0.57	P
Vest4		0.45
MutPred		0.19		Gain of glycosylation at H319 (P = 0.0898)
MVP		0.57
ClinPred		0.47	T
GERP RS		4.6
Varity_R		0.54
gMVP		0.60

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: rs778638603; hg19: chr17-37761897;