2-229388294-T-C

Position:

• chr2-229388294-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_139072.4(DNER):​c.1826A>G​(p.His609Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,458,716 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: DNER NM_139072.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.72

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37461773).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNER	NM_139072.4	c.1826A>G	p.His609Arg	missense_variant	11/13	ENST00000341772.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNER	ENST00000341772.5	c.1826A>G	p.His609Arg	missense_variant	11/13	1	NM_139072.4	P1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1458716 Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 2 AN XY: 725696

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.41	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.064
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.72	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.35	T
MutationAssessor	Benign	-0.32	N
MutationTaster	Benign	0.99	D
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.0	N
REVEL	Uncertain	0.30
Sift	Benign	0.41	T
Sift4G	Benign	0.23	T
Polyphen		0.66	P
Vest4		0.32
MutPred		0.52		Loss of disorder (P = 0.3371);
MVP		0.71
MPC		0.16
ClinPred		0.78	D
GERP RS		3.3
Varity_R		0.14
gMVP		0.54

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-230253010;