2-229485273-T-C

Variant names:

• chr2-229485273-T-C
• rs11890081
• NM_139072.4:c.1148-8020A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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 (AFR) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139072.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNER	NM_139072.4	MANE Select	c.1148-8020A>G		intron	N/A	NP_620711.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNER	ENST00000341772.5	TSL:1 MANE Select	c.1148-8020A>G		intron	N/A	ENSP00000345229.4

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

African (AFR) AF: 0.210 AC: 8719 AN: 41480

American (AMR) AF: 0.0285 AC: 436 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0127 AC: 44 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00581 AC: 28 AN: 4820

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10612

Middle Eastern (MID) AF: 0.0616 AC: 18 AN: 292

European-Non Finnish (NFE) AF: 0.00603 AC: 410 AN: 68008

Other (OTH) AF: 0.0482 AC: 102 AN: 2114

Alfa AF: 0.0595 Hom.: 515

Bravo AF: 0.0725

Asia WGS AF: 0.0130 AC: 46 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.17
DANN	Benign	0.47
PhyloP100		-0.65
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: rs11890081; hg19: chr2-230349989;