NM_015086.2:c.163A>G

Variant names:

• chr12-48999125-T-C
• rs774638950
• NM_015086.2:c.163A>G

Variant summary

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

The NM_015086.2(DDN):​c.163A>G​(p.Met55Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,848 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M55L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: DDN NM_015086.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39
• Publications: 1 publications found

Genes affected

DDN (HGNC:24458): (dendrin) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to act upstream of or within positive regulation of transcription by RNA polymerase II. Located in cell projection and cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

DDN-AS1 (HGNC:53464): (DDN and PRKAG1 antisense RNA 1)

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_015086.2. 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
	DDN	NM_015086.2	MANE Select	c.163A>G	p.Met55Val	missense	Exon 1 of 2	NP_055901.2	O94850
	DDN-AS1	NR_147178.1		n.344+435T>C		intron	N/A
	DDN-AS1	NR_147179.1		n.344+435T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDN	ENST00000421952.3	TSL:1 MANE Select	c.163A>G	p.Met55Val	missense	Exon 1 of 2	ENSP00000390590.2	O94850
	DDN-AS1	ENST00000547395.1	TSL:2	n.293+435T>C		intron	N/A
	DDN-AS1	ENST00000547866.1	TSL:3	n.319+435T>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251054 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461848 Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3 AN XY: 727232

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

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

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

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111984

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.19
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.55	T
M_CAP	Uncertain	0.099	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.4
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.26	T
Polyphen		0.95	P
Vest4		0.53
MutPred		0.21		Gain of catalytic residue at F57 (P = 0.0502)
MVP		0.48
MPC		1.6
ClinPred		0.94	D
GERP RS		3.7
PromoterAI		0.046	Neutral
Varity_R		0.78
gMVP		0.11
Mutation Taster		=81/19	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: rs774638950; hg19: chr12-49392908;