Genetic Variant DDAH2:c.-325A>C (chr6-31730311-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000375792.7(DDAH2):c.-325A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 178,096 control chromosomes in the GnomAD database, including 20,589 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.48 ( 18854 hom., cov: 34)

Exomes 𝑓: 0.35 ( 1735 hom. )

Consequence

DDAH2
ENST00000375792.7 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.601

Publications

49 publications found

Variant links:

Genes affected

DDAH2 (HGNC:2716): (DDAH family member 2, ADMA-independent) This gene encodes a dimethylarginine dimethylaminohydrolase. The encoded enzyme functions in nitric oxide generation by regulating the cellular concentrations of methylarginines, which in turn inhibit nitric oxide synthase activity. The protein may be localized to the mitochondria. Alternative splicing resulting in multiple transcript variants. [provided by RefSeq, Dec 2014]

DDAH2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000375792.7. 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
	DDAH2	NM_013974.3		c.-325A>C		upstream_gene	N/A	NP_039268.1	O95865

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DDAH2	ENST00000375792.7	TSL:1	c.-325A>C	5_prime_UTR	Exon 1 of 7	ENSP00000364949.3	O95865
DDAH2	ENST00000857391.1		c.-325A>C	upstream_gene	N/A	ENSP00000527450.1
DDAH2	ENST00000375787.6	TSL:5	c.-321A>C	upstream_gene	N/A	ENSP00000364943.2	O95865

Frequencies

GnomAD3 genomes

AF:

0.475

AC:

72273

AN:

152016

Hom.:

18819

Cov.:

show subpopulations

Gnomad AFR

AF:

0.706

Gnomad AMI

AF:

0.278

Gnomad AMR

AF:

0.442

Gnomad ASJ

AF:

0.341

Gnomad EAS

AF:

0.401

Gnomad SAS

AF:

0.447

Gnomad FIN

AF:

0.485

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.359

Gnomad OTH

AF:

0.470

GnomAD4 exome

AF:

0.346

AC:

8993

AN:

25962

Hom.:

1735

Cov.:

AF XY:

0.344

AC XY:

4658

AN XY:

13536

show subpopulations

African (AFR)

AF:

0.705

AC:

420

AN:

596

American (AMR)

AF:

0.383

AC:

259

AN:

676

Ashkenazi Jewish (ASJ)

AF:

0.315

AC:

236

AN:

750

East Asian (EAS)

AF:

0.345

AC:

812

AN:

2352

South Asian (SAS)

AF:

0.396

AC:

286

AN:

722

European-Finnish (FIN)

AF:

0.441

AC:

1181

AN:

2678

Middle Eastern (MID)

AF:

0.326

AC:

AN:

144

European-Non Finnish (NFE)

AF:

0.313

AC:

5207

AN:

16638

Other (OTH)

AF:

0.388

AC:

545

AN:

1406

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

271

542

813

1084

1355

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.476

AC:

72358

AN:

152134

Hom.:

18854

Cov.:

AF XY:

0.478

AC XY:

35568

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.706

AC:

29295

AN:

41518

American (AMR)

AF:

0.442

AC:

6760

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.341

AC:

1183

AN:

3470

East Asian (EAS)

AF:

0.401

AC:

2067

AN:

5158

South Asian (SAS)

AF:

0.446

AC:

2154

AN:

4826

European-Finnish (FIN)

AF:

0.485

AC:

5134

AN:

10590

Middle Eastern (MID)

AF:

0.446

AC:

131

AN:

294

European-Non Finnish (NFE)

AF:

0.359

AC:

24381

AN:

67954

Other (OTH)

AF:

0.473

AC:

1000

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1846

3693

5539

7386

9232

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

624

1248

1872

2496

3120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.443

Hom.:

21706

Bravo

AF:

0.483

Asia WGS

AF:

0.520

AC:

1805

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

4.8

(source)

DANN

Benign

0.67

PhyloP100

-0.60

PromoterAI

0.0060

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over