rs1801262

chr2-181678728-T-Achr2-181678728-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002500.5(NEUROD1):c.133A>T(p.Thr45Ser) 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. 16/21 in silico tools predict 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. T45A) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NEUROD1 NM_002500.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.563

Genes affected

NEUROD1 (HGNC:7762): (neuronal differentiation 1) This gene encodes a member of the NeuroD family of basic helix-loop-helix (bHLH) transcription factors. The protein forms heterodimers with other bHLH proteins and activates transcription of genes that contain a specific DNA sequence known as the E-box. It regulates expression of the insulin gene, and mutations in this gene result in type II diabetes mellitus. [provided by RefSeq, Jul 2008]

CERKL (HGNC:21699): (ceramide kinase like) This gene was initially identified as a locus (RP26) associated with an autosomal recessive form of retinitis pigmentosa (arRP) disease. This gene encodes a protein with ceramide kinase-like domains, however, the protein does not phosphorylate ceramide and its target substrate is currently unknown. This protein may be a negative regulator of apoptosis in photoreceptor cells. Mutations in this gene cause a form of retinitis pigmentosa characterized by autosomal recessive cone and rod dystrophy (arCRD). Alternative splicing of this gene results in multiple transcript variants encoding different isoforms and non-coding transcripts.[provided by RefSeq, May 2010]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044108182).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEUROD1	NM_002500.5	c.133A>T	p.Thr45Ser	missense_variant	2/2	ENST00000295108.4
NEUROD1	NR_146175.2	n.88+1702A>T		intron_variant, non_coding_transcript_variant
NEUROD1	NR_146176.2	n.88+1702A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEUROD1	ENST00000295108.4	c.133A>T	p.Thr45Ser	missense_variant	2/2	1	NM_002500.5	P1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1459328 Hom.: 0 Cov.: 73 AF XY: 0.00 AC XY: 0 AN XY: 725720

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
Cadd	Benign	9.5
Dann	Benign	0.80
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.0015	N
LIST_S2	Benign	0.13	T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	-0.69	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.41	N
REVEL	Benign	0.23
Sift	Benign	0.78	T
Sift4G	Benign	0.77	T
Polyphen		0.0	B
Vest4		0.019
MutPred		0.19		Gain of phosphorylation at T45 (P = 0.0592);
MVP		0.83
MPC		0.41
ClinPred		0.038	T
GERP RS		4.4
Varity_R		0.061
gMVP		0.069

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

LitVar

Other links and lift over

dbSNP: rs1801262; hg19: chr2-182543455;