17-39605587-GTGGGC-G

Variant names:

• chr17-39605587-GTGGGC-G
• NM_006160.4:c.1008_1012delGCCCA

Variant summary

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

The NM_006160.4(NEUROD2):​c.1008_1012delGCCCA​(p.Pro337GlyfsTer44) variant causes a frameshift 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 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.16
• 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.1008_1012delGCCCA	p.Pro337GlyfsTer44	frameshift	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.1008_1012delGCCCA	p.Pro337GlyfsTer44	frameshift	Exon 2 of 2	ENSP00000306754.4	Q15784
	NEUROD2	ENST00000907630.1		c.1008_1012delGCCCA	p.Pro337GlyfsTer44	frameshift	Exon 2 of 2	ENSP00000577689.1
	NEUROD2	ENST00000907631.1		c.1008_1012delGCCCA	p.Pro337GlyfsTer44	frameshift	Exon 2 of 2	ENSP00000577690.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

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
PhyloP100		6.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr17-37761840;