rs1861612

Variant names:

• chr2-229657682-G-A
• rs1861612
• NM_139072.4:c.276+56466C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-229657682-G-A
• chr2-229657682-G-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.276+56466C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 151,996 control chromosomes in the GnomAD database, including 21,128 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 0.52 (21128 hom., cov: 32)
• Consequence: DNER NM_139072.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.287
• Publications: 33 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNER	NM_139072.4	c.276+56466C>T		intron_variant	Intron 1 of 12	ENST00000341772.5	NP_620711.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNER	ENST00000341772.5	c.276+56466C>T		intron_variant	Intron 1 of 12	1	NM_139072.4	ENSP00000345229.4

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79673 AN: 151878 Hom.: 21110 Cov.: 32

Gnomad AFR AF: 0.518

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.536

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

GnomAD4 genome AF: 0.525 AC: 79734 AN: 151996 Hom.: 21128 Cov.: 32 AF XY: 0.521 AC XY: 38706 AN XY: 74272

African (AFR) AF: 0.518 AC: 21458 AN: 41440

American (AMR) AF: 0.533 AC: 8132 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 1482 AN: 3468

East Asian (EAS) AF: 0.459 AC: 2369 AN: 5160

South Asian (SAS) AF: 0.493 AC: 2371 AN: 4814

European-Finnish (FIN) AF: 0.447 AC: 4717 AN: 10562

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.550 AC: 37360 AN: 67972

Other (OTH) AF: 0.530 AC: 1118 AN: 2110

Alfa AF: 0.540 Hom.: 96547

Bravo AF: 0.532

Asia WGS AF: 0.443 AC: 1543 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	1.8
DANN	Benign	0.70
PhyloP100		-0.29
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: rs1861612; hg19: chr2-230522398;