chr2-229578860-A-G

Variant names:

• chr2-229578860-A-G
• rs10519389
• NM_139072.4:c.847+6998T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139072.4(DNER):​c.847+6998T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,240 control chromosomes in the GnomAD database, including 2,678 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 0.12 (2678 hom., cov: 32)
• Consequence: DNER NM_139072.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.182
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNER	NM_139072.4	c.847+6998T>C		intron_variant	Intron 4 of 12	ENST00000341772.5	NP_620711.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNER	ENST00000341772.5	c.847+6998T>C		intron_variant	Intron 4 of 12	1	NM_139072.4	ENSP00000345229.4

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18910 AN: 152122 Hom.: 2653 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.0851

Gnomad ASJ AF: 0.0836

Gnomad EAS AF: 0.0208

Gnomad SAS AF: 0.0563

Gnomad FIN AF: 0.0135

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0327

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.125 AC: 18972 AN: 152240 Hom.: 2678 Cov.: 32 AF XY: 0.122 AC XY: 9112 AN XY: 74452

African (AFR) AF: 0.344 AC: 14287 AN: 41496

American (AMR) AF: 0.0849 AC: 1299 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0836 AC: 290 AN: 3468

East Asian (EAS) AF: 0.0208 AC: 108 AN: 5186

South Asian (SAS) AF: 0.0555 AC: 268 AN: 4826

European-Finnish (FIN) AF: 0.0135 AC: 143 AN: 10626

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0328 AC: 2229 AN: 68026

Other (OTH) AF: 0.113 AC: 239 AN: 2112

Alfa AF: 0.0772 Hom.: 472

Bravo AF: 0.141

Asia WGS AF: 0.0460 AC: 161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.1
DANN	Benign	0.66
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

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: rs10519389; hg19: chr2-230443576;