rs10783299

chr12-48996894-T-Cchr12-48996894-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015086.2(DDN):c.1982A>G(p.Glu661Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 1,613,036 control chromosomes in the GnomAD database, including 126,965 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.42 (13821 hom., cov: 33)
  • Exomes 𝑓: 0.39 (113144 hom.)
• Consequence: DDN NM_015086.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.769

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.3861852E-5).
• BP6: Variant 12-48996894-T-C is Benign according to our data. Variant chr12-48996894-T-C is described in ClinVar as [Benign]. Clinvar id is 1244708.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDN	NM_015086.2	c.1982A>G	p.Glu661Gly	missense_variant	2/2	ENST00000421952.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDN	ENST00000421952.3	c.1982A>G	p.Glu661Gly	missense_variant	2/2	1	NM_015086.2	P1

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63804 AN: 151988 Hom.: 13788 Cov.: 33

Gnomad AFR AF: 0.518

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.380

GnomAD3 exomes AF: 0.384 AC: 95542 AN: 248894 Hom.: 18908 AF XY: 0.386 AC XY: 52030 AN XY: 134692

Gnomad AFR exome AF: 0.525

Gnomad AMR exome AF: 0.274

Gnomad ASJ exome AF: 0.251

Gnomad EAS exome AF: 0.438

Gnomad SAS exome AF: 0.434

Gnomad FIN exome AF: 0.414

Gnomad NFE exome AF: 0.382

Gnomad OTH exome AF: 0.370

GnomAD4 exome AF: 0.390 AC: 570105 AN: 1460928 Hom.: 113144 Cov.: 63 AF XY: 0.390 AC XY: 283779 AN XY: 726766

Gnomad4 AFR exome AF: 0.526

Gnomad4 AMR exome AF: 0.281

Gnomad4 ASJ exome AF: 0.255

Gnomad4 EAS exome AF: 0.397

Gnomad4 SAS exome AF: 0.429

Gnomad4 FIN exome AF: 0.413

Gnomad4 NFE exome AF: 0.390

Gnomad4 OTH exome AF: 0.393

GnomAD4 genome AF: 0.420 AC: 63896 AN: 152108 Hom.: 13821 Cov.: 33 AF XY: 0.418 AC XY: 31103 AN XY: 74372

Gnomad4 AFR AF: 0.519

Gnomad4 AMR AF: 0.343

Gnomad4 ASJ AF: 0.245

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.451

Gnomad4 FIN AF: 0.413

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.379

Alfa AF: 0.382 Hom.: 28925

Bravo AF: 0.412

TwinsUK AF: 0.379 AC: 1407

ALSPAC AF: 0.400 AC: 1543

ESP6500AA AF: 0.512 AC: 2254

ESP6500EA AF: 0.373 AC: 3211

ExAC AF: 0.387 AC: 47019

Asia WGS AF: 0.438 AC: 1521 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 26, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.048
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.81
Cadd	Benign	6.3
Dann	Benign	0.69
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0037	N
LIST_S2	Benign	0.12	T
MetaRNN	Benign	0.000024	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.29	T
PROVEAN	Benign	2.3	N
REVEL	Benign	0.029
Sift	Benign	0.75	T
Sift4G	Benign	0.39	T
Polyphen		0.0	B
Vest4		0.0080
MPC		0.74
ClinPred		0.00095	T
GERP RS		-5.8
Varity_R		0.025
gMVP		0.019

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

LitVar

Other links and lift over

dbSNP: rs10783299; hg19: chr12-49390677; COSMIC: COSV70404325; COSMIC: COSV70404325;