Genetic Variant DDAH2:c.-64-385G>C (chr6-31729610-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_013974.3(DDAH2):c.-64-385G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 186,142 control chromosomes in the GnomAD database, including 21,517 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 ( 18841 hom., cov: 32)

Exomes 𝑓: 0.38 ( 2676 hom. )

Consequence

DDAH2
NM_013974.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.795

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=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013974.3. 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.-64-385G>C		intron	N/A	NP_039268.1	O95865
	DDAH2	NM_001303008.2		c.-313G>C		upstream_gene	N/A	NP_001289937.1	O95865

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DDAH2	ENST00000375792.7	TSL:1	c.-64-385G>C	intron	N/A	ENSP00000364949.3	O95865
DDAH2	ENST00000921344.1		c.-449G>C	5_prime_UTR	Exon 1 of 6	ENSP00000591403.1
DDAH2	ENST00000970328.1		c.-449G>C	5_prime_UTR	Exon 1 of 5	ENSP00000640387.1

Frequencies

GnomAD3 genomes

AF:

0.476

AC:

72189

AN:

151808

Hom.:

18806

Cov.:

show subpopulations

Gnomad AFR

AF:

0.707

Gnomad AMI

AF:

0.277

Gnomad AMR

AF:

0.442

Gnomad ASJ

AF:

0.341

Gnomad EAS

AF:

0.401

Gnomad SAS

AF:

0.446

Gnomad FIN

AF:

0.484

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.359

Gnomad OTH

AF:

0.471

GnomAD4 exome

AF:

0.381

AC:

13039

AN:

34216

Hom.:

2676

Cov.:

AF XY:

0.382

AC XY:

6787

AN XY:

17790

show subpopulations

African (AFR)

AF:

0.698

AC:

673

AN:

964

American (AMR)

AF:

0.429

AC:

1342

AN:

3128

Ashkenazi Jewish (ASJ)

AF:

0.357

AC:

351

AN:

984

East Asian (EAS)

AF:

0.382

AC:

622

AN:

1630

South Asian (SAS)

AF:

0.426

AC:

1295

AN:

3038

European-Finnish (FIN)

AF:

0.440

AC:

639

AN:

1452

Middle Eastern (MID)

AF:

0.382

AC:

AN:

136

European-Non Finnish (NFE)

AF:

0.347

AC:

7263

AN:

20944

Other (OTH)

AF:

0.413

AC:

802

AN:

1940

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

390

779

1169

1558

1948

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

136

272

408

544

680

<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:

72274

AN:

151926

Hom.:

18841

Cov.:

AF XY:

0.478

AC XY:

35506

AN XY:

74236

show subpopulations

African (AFR)

AF:

0.707

AC:

29295

AN:

41446

American (AMR)

AF:

0.442

AC:

6744

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.341

AC:

1181

AN:

3466

East Asian (EAS)

AF:

0.401

AC:

2069

AN:

5158

South Asian (SAS)

AF:

0.446

AC:

2138

AN:

4798

European-Finnish (FIN)

AF:

0.484

AC:

5101

AN:

10540

Middle Eastern (MID)

AF:

0.446

AC:

131

AN:

294

European-Non Finnish (NFE)

AF:

0.359

AC:

24362

AN:

67944

Other (OTH)

AF:

0.474

AC:

1000

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1808

3615

5423

7230

9038

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

622

1244

1866

2488

3110

<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:

0.414

Hom.:

1893

Bravo

AF:

0.483

Asia WGS

AF:

0.521

AC:

1807

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

7.4

(source)

DANN

Benign

0.60

PhyloP100

0.80

PromoterAI

-0.013

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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