chr2-229653517-A-G

Position:

• chr2-229653517-A-G

Variant summary

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

The NM_139072.4(DNER):​c.276+60631T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,100 control chromosomes in the GnomAD database, including 4,818 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 0.24 (4818 hom., cov: 33)
• Consequence: DNER NM_139072.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.810

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNER	NM_139072.4	c.276+60631T>C		intron_variant		ENST00000341772.5	NP_620711.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNER	ENST00000341772.5	c.276+60631T>C		intron_variant		1	NM_139072.4	ENSP00000345229.4

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36538 AN: 151982 Hom.: 4794 Cov.: 33

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.241 AC: 36607 AN: 152100 Hom.: 4818 Cov.: 33 AF XY: 0.244 AC XY: 18172 AN XY: 74340

Gnomad4 AFR AF: 0.341

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.261

Gnomad4 SAS AF: 0.286

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.252

Alfa AF: 0.192 Hom.: 6157

Bravo AF: 0.237

Asia WGS AF: 0.314 AC: 1091 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.20
DANN	Benign	0.82

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: rs6752370; hg19: chr2-230518233;