17-39605523-CAAG-C

Variant names:

• chr17-39605523-CAAG-C
• NM_006160.4:c.1074_1076delCTT

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PM4_Supporting

The NM_006160.4(NEUROD2):​c.1074_1076delCTT​(p.Leu359del) variant causes a disruptive inframe deletion 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 disruptive_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.92

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_006160.4. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEUROD2	NM_006160.4	c.1074_1076delCTT	p.Leu359del	disruptive_inframe_deletion	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.1074_1076delCTT	p.Leu359del	disruptive_inframe_deletion	Exon 2 of 2	1	NM_006160.4	ENSP00000306754.4
NEUROD2	ENST00000580874.1	n.4252_4254delCTT		non_coding_transcript_exon_variant	Exon 1 of 1	6

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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Jun 21, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1074_1076delCTT (p.L359del) alteration is located in exon 2 (coding exon 1) of the NEUROD2 gene. This alteration consists of an in-frame deletion of 3 nucleotides between nucleotide positions c.1074 and c.1076, resulting in the deletion of <NA> residues. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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: chr17-37761776;