rs10783299

Variant names:

• chr12-48996894-T-C
• rs10783299
• NM_015086.2:c.1982A>G

Your query was ambiguous. Multiple possible variants found:

• chr12-48996894-T-C
• chr12-48996894-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E661D) has been classified as Uncertain significance.

• 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.769
• Publications: 46 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]

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1244708.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDN	NM_015086.2	MANE Select	c.1982A>G	p.Glu661Gly	missense	Exon 2 of 2	NP_055901.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDN	ENST00000421952.3	TSL:1 MANE Select	c.1982A>G	p.Glu661Gly	missense	Exon 2 of 2	ENSP00000390590.2

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

GnomAD2 exomes AF: 0.384 AC: 95542 AN: 248894 AF XY: 0.386

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 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

African (AFR) AF: 0.526 AC: 17598 AN: 33464

American (AMR) AF: 0.281 AC: 12485 AN: 44504

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 6658 AN: 26102

East Asian (EAS) AF: 0.397 AC: 15775 AN: 39688

South Asian (SAS) AF: 0.429 AC: 36985 AN: 86204

European-Finnish (FIN) AF: 0.413 AC: 22017 AN: 53344

Middle Eastern (MID) AF: 0.287 AC: 1655 AN: 5764

European-Non Finnish (NFE) AF: 0.390 AC: 433231 AN: 1111516

Other (OTH) AF: 0.393 AC: 23701 AN: 60342

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

African (AFR) AF: 0.519 AC: 21530 AN: 41486

American (AMR) AF: 0.343 AC: 5243 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 848 AN: 3468

East Asian (EAS) AF: 0.426 AC: 2196 AN: 5160

South Asian (SAS) AF: 0.451 AC: 2171 AN: 4812

European-Finnish (FIN) AF: 0.413 AC: 4375 AN: 10586

Middle Eastern (MID) AF: 0.271 AC: 79 AN: 292

European-Non Finnish (NFE) AF: 0.387 AC: 26328 AN: 67984

Other (OTH) AF: 0.379 AC: 802 AN: 2116

Alfa AF: 0.389 Hom.: 43136

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		-0.77
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
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: rs10783299; hg19: chr12-49390677; COSMIC: COSV70404325; COSMIC: COSV70404325;