2-229359315-T-C

Variant names:

• chr2-229359315-T-C
• rs7594321
• NM_139072.4:c.2103-664A>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.2103-664A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 152,126 control chromosomes in the GnomAD database, including 39,992 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 0.72 (39992 hom., cov: 32)
• Consequence: DNER NM_139072.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270
• Publications: 9 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.885 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNER	NM_139072.4	MANE Select	c.2103-664A>G		intron	N/A	NP_620711.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNER	ENST00000341772.5	TSL:1 MANE Select	c.2103-664A>G		intron	N/A	ENSP00000345229.4	Q8NFT8
	DNER	ENST00000898999.1		c.2235-664A>G		intron	N/A	ENSP00000569058.1
	DNER	ENST00000898995.1		c.2166-664A>G		intron	N/A	ENSP00000569054.1

Frequencies

GnomAD3 genomes AF: 0.719 AC: 109301 AN: 152008 Hom.: 39942 Cov.: 32

Gnomad AFR AF: 0.826

Gnomad AMI AF: 0.626

Gnomad AMR AF: 0.755

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.906

Gnomad SAS AF: 0.673

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.707

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

GnomAD4 genome AF: 0.719 AC: 109411 AN: 152126 Hom.: 39992 Cov.: 32 AF XY: 0.721 AC XY: 53613 AN XY: 74376

African (AFR) AF: 0.826 AC: 34269 AN: 41504

American (AMR) AF: 0.755 AC: 11546 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 2356 AN: 3472

East Asian (EAS) AF: 0.906 AC: 4687 AN: 5172

South Asian (SAS) AF: 0.671 AC: 3242 AN: 4828

European-Finnish (FIN) AF: 0.659 AC: 6955 AN: 10560

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.649 AC: 44091 AN: 67986

Other (OTH) AF: 0.709 AC: 1497 AN: 2110

Alfa AF: 0.679 Hom.: 53926

Bravo AF: 0.733

Asia WGS AF: 0.798 AC: 2771 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.7
DANN	Benign	0.34
PhyloP100		-0.027
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: rs7594321; hg19: chr2-230224031;