rs10197959

Positions:

• chr2-229505398-C-A

Variant summary

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

The NM_139072.4(DNER):​c.1147+7385G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 151,910 control chromosomes in the GnomAD database, including 10,771 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 0.36 (10771 hom., cov: 31)
• Consequence: DNER NM_139072.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.453

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 (NFE) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNER	NM_139072.4	c.1147+7385G>T		intron_variant		ENST00000341772.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNER	ENST00000341772.5	c.1147+7385G>T		intron_variant		1	NM_139072.4	P1

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55370 AN: 151792 Hom.: 10769 Cov.: 31

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.348

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

GnomAD4 genome AF: 0.364 AC: 55370 AN: 151910 Hom.: 10771 Cov.: 31 AF XY: 0.365 AC XY: 27077 AN XY: 74234

Gnomad4 AFR AF: 0.240

Gnomad4 AMR AF: 0.341

Gnomad4 ASJ AF: 0.389

Gnomad4 EAS AF: 0.247

Gnomad4 SAS AF: 0.429

Gnomad4 FIN AF: 0.457

Gnomad4 NFE AF: 0.433

Gnomad4 OTH AF: 0.343

Alfa AF: 0.410 Hom.: 18545

Bravo AF: 0.348

Asia WGS AF: 0.312 AC: 1084 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	2.4
DANN	Benign	0.46

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: rs10197959; hg19: chr2-230370114;