dbSNP rs707916: DDAH2:c.-65+270C>T (chr6-31729781-G-A) – 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.-65+270C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 153,686 control chromosomes in the GnomAD database, including 19,029 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 ( 18856 hom., cov: 31)

Exomes 𝑓: 0.40 ( 173 hom. )

Consequence

DDAH2
ENST00000375792.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.307

Publications

35 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:

Genome browser will be placed here

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=-0.71).

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDAH2	XM_011514448.3 link	c.-163C>T		5_prime_UTR_variant	Exon 1 of 7		XP_011512750.1
DDAH2	NM_013974.3 link	c.-65+270C>T		intron_variant	Intron 1 of 6		NP_039268.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
DDAH2	ENST00000375792.7 link	c.-65+270C>T	intron_variant	Intron 1 of 6	1	ENSP00000364949.3
DDAH2	ENST00000416410.6 link	c.-163C>T	5_prime_UTR_variant	Exon 1 of 7	2	ENSP00000397466.2
DDAH2	ENST00000375787.6 link	c.-61+270C>T	intron_variant	Intron 1 of 6	5	ENSP00000364943.2

Frequencies

GnomAD3 genomes

AF:

0.476

AC:

72214

AN:

151816

Hom.:

18821

Cov.:

show subpopulations

Gnomad AFR

AF:

0.707

Gnomad AMI

AF:

0.278

Gnomad AMR

AF:

0.441

Gnomad ASJ

AF:

0.341

Gnomad EAS

AF:

0.399

Gnomad SAS

AF:

0.446

Gnomad FIN

AF:

0.487

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.359

Gnomad OTH

AF:

0.471

GnomAD4 exome

AF:

0.402

AC:

705

AN:

1752

Hom.:

173

Cov.:

AF XY:

0.386

AC XY:

371

AN XY:

962

show subpopulations

African (AFR)

AF:

0.750

AC:

AN:

American (AMR)

AF:

0.507

AC:

147

AN:

290

Ashkenazi Jewish (ASJ)

AF:

0.200

AC:

AN:

East Asian (EAS)

AF:

0.300

AC:

AN:

South Asian (SAS)

AF:

0.416

AC:

109

AN:

262

European-Finnish (FIN)

AF:

0.438

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.369

AC:

398

AN:

1078

Other (OTH)

AF:

0.382

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.535

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

72299

AN:

151934

Hom.:

18856

Cov.:

AF XY:

0.479

AC XY:

35539

AN XY:

74228

show subpopulations

African (AFR)

AF:

0.707

AC:

29307

AN:

41460

American (AMR)

AF:

0.441

AC:

6737

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.341

AC:

1183

AN:

3472

East Asian (EAS)

AF:

0.399

AC:

2058

AN:

5152

South Asian (SAS)

AF:

0.445

AC:

2143

AN:

4816

European-Finnish (FIN)

AF:

0.487

AC:

5119

AN:

10518

Middle Eastern (MID)

AF:

0.446

AC:

131

AN:

294

European-Non Finnish (NFE)

AF:

0.359

AC:

24373

AN:

67950

Other (OTH)

AF:

0.474

AC:

995

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1777

3554

5332

7109

8886

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:

0.439

Hom.:

19603

Bravo

AF:

0.483

Asia WGS

AF:

0.519

AC:

1802

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

1.9

(source)

DANN

Benign

0.88

PhyloP100

-0.31

PromoterAI

-0.050

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over