2-181677112-A-ATTTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_002500.5(NEUROD1):c.*677_*678insAAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2168 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NEUROD1 NM_002500.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.959

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 Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEUROD1	NM_002500.5	c.*677_*678insAAAA		3_prime_UTR_variant	2/2	ENST00000295108.4
NEUROD1	NR_146175.2	n.88+3317_88+3318insAAAA		intron_variant, non_coding_transcript_variant
NEUROD1	NR_146176.2	n.88+3317_88+3318insAAAA		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEUROD1	ENST00000295108.4	c.*677_*678insAAAA		3_prime_UTR_variant	2/2	1	NM_002500.5	P1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 7723 AN: 49302 Hom.: 2167 Cov.: 0

Gnomad AFR AF: 0.0577

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.0592

Gnomad SAS AF: 0.0627

Gnomad FIN AF: 0.0748

Gnomad MID AF: 0.0313

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.160

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 80 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 50

Gnomad4 FIN exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.157 AC: 7725 AN: 49324 Hom.: 2168 Cov.: 0 AF XY: 0.148 AC XY: 3189 AN XY: 21516

Gnomad4 AFR AF: 0.0578

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.0592

Gnomad4 SAS AF: 0.0628

Gnomad4 FIN AF: 0.0748

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.159

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Maturity onset diabetes mellitus in young Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs374172497; hg19: chr2-182541839;