rs11890081

Positions:

• chr2-229485273-T-C
• chr2-229485273-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139072.4(DNER):​c.1148-8020A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0641 in 152,174 control chromosomes in the GnomAD database, including 949 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.064 (949 hom., cov: 32)
• Consequence: DNER NM_139072.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.646

Genes affected

DNER (HGNC:24456): (delta/notch like EGF repeat containing) Predicted to enable Notch binding activity. Involved in central nervous system development. Located in dendrite; early endosome; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNER	NM_139072.4	c.1148-8020A>G		intron_variant		ENST00000341772.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNER	ENST00000341772.5	c.1148-8020A>G		intron_variant		1	NM_139072.4	P1

Frequencies

GnomAD3 genomes AF: 0.0641 AC: 9740 AN: 152056 Hom.: 943 Cov.: 32

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0286

Gnomad ASJ AF: 0.0127

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00580

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.0573

Gnomad NFE AF: 0.00603

Gnomad OTH AF: 0.0488

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

GnomAD4 genome AF: 0.0641 AC: 9759 AN: 152174 Hom.: 949 Cov.: 32 AF XY: 0.0614 AC XY: 4569 AN XY: 74422

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.0285

Gnomad4 ASJ AF: 0.0127

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00581

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.00603

Gnomad4 OTH AF: 0.0482

Alfa AF: 0.00949 Hom.: 20

Bravo AF: 0.0725

Asia WGS AF: 0.0130 AC: 46 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.17
DANN	Benign	0.47

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: rs11890081; hg19: chr2-230349989;