17-39605880-C-T

Variant names:

• chr17-39605880-C-T
• rs1482364255
• NM_006160.4:c.720G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_006160.4(NEUROD2):​c.720G>A​(p.Pro240Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000704 in 1,420,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P240P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: NEUROD2 NM_006160.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.229
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP7: Synonymous conserved (PhyloP=-0.229 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEUROD2	NM_006160.4	c.720G>A	p.Pro240Pro	synonymous_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.720G>A	p.Pro240Pro	synonymous_variant	Exon 2 of 2	1	NM_006160.4	ENSP00000306754.4
NEUROD2	ENST00000580874.1	n.3898G>A		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.04e-7 AC: 1 AN: 1420176 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 704950

African (AFR) AF: 0.0000318 AC: 1 AN: 31494

American (AMR) AF: 0.00 AC: 0 AN: 39724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24718

East Asian (EAS) AF: 0.00 AC: 0 AN: 37018

South Asian (SAS) AF: 0.00 AC: 0 AN: 81610

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46734

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5430

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1094840

Other (OTH) AF: 0.00 AC: 0 AN: 58608

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	9.6
DANN	Benign	0.94
PhyloP100		-0.23

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: rs1482364255; hg19: chr17-37762133;