NM_023932.4:c.854G>T

Variant names:

• chr6-43450837-C-A
• rs1309688551
• NM_023932.4:c.854G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_023932.4(DLK2):​c.854G>T​(p.Gly285Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000867 in 1,614,064 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: DLK2 NM_023932.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.67
• Publications: 1 publications found

Genes affected

DLK2 (HGNC:21113): (delta like non-canonical Notch ligand 2) Predicted to enable Notch binding activity. Involved in negative regulation of Notch signaling pathway. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ABCC10 (HGNC:52): (ATP binding cassette subfamily C member 10) The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, and White). This ABC full-transporter is a member of the MRP subfamily which is involved in multi-drug resistance. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Nov 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023932.4. 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
	DLK2	NM_023932.4	MANE Select	c.854G>T	p.Gly285Val	missense	Exon 6 of 6	NP_076421.2
	DLK2	NM_206539.2		c.854G>T	p.Gly285Val	missense	Exon 6 of 6	NP_996262.1	Q6UY11-1
	DLK2	NM_001286656.2		c.836G>T	p.Gly279Val	missense	Exon 6 of 6	NP_001273585.1	Q5T3T9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLK2	ENST00000372488.8	TSL:1 MANE Select	c.854G>T	p.Gly285Val	missense	Exon 6 of 6	ENSP00000361566.3	Q6UY11-1
	DLK2	ENST00000357338.3	TSL:2	c.854G>T	p.Gly285Val	missense	Exon 6 of 6	ENSP00000349893.3	Q6UY11-1
	DLK2	ENST00000854537.1		c.854G>T	p.Gly285Val	missense	Exon 5 of 5	ENSP00000524596.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152214 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000889 AC: 13 AN: 1461850 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727228

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1111994

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152214 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74350

African (AFR) AF: 0.00 AC: 0 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	T
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.055	D
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.0	L
PhyloP100		5.7
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.64
Sift	Uncertain	0.029	D
Sift4G	Uncertain	0.044	D
Polyphen		1.0	D
Vest4		0.58
MutPred		0.54		Gain of sheet (P = 4e-04)
MVP		0.52
MPC		1.2
ClinPred		0.97	D
GERP RS		5.2
Varity_R		0.37
gMVP		0.72
Mutation Taster		=70/30	polymorphism

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: rs1309688551; hg19: chr6-43418575;