6-31729151-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001303007.2(DDAH2):c.11C>G(p.Pro4Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00219 in 1,606,010 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.012 ( 28 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 24 hom. )

Consequence

DDAH2
NM_001303007.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.04

Publications

0 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0043207705).

BP6

Variant 6-31729151-G-C is Benign according to our data. Variant chr6-31729151-G-C is described in ClinVar as [Benign]. Clinvar id is 786084.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0118 (1795/151522) while in subpopulation AFR AF = 0.0401 (1656/41308). AF 95% confidence interval is 0.0385. There are 28 homozygotes in GnomAd4. There are 813 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 1795 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDAH2	NM_001303007.2 link	c.11C>G	p.Pro4Arg	missense_variant	Exon 1 of 6	ENST00000375789.7	NP_001289936.1	O95865V9HW53
DDAH2	NM_001303008.2 link	c.11C>G	p.Pro4Arg	missense_variant	Exon 2 of 7		NP_001289937.1	O95865V9HW53
DDAH2	NM_013974.3 link	c.11C>G	p.Pro4Arg	missense_variant	Exon 2 of 7		NP_039268.1	O95865V9HW53
DDAH2	XM_011514448.3 link	c.11C>G	p.Pro4Arg	missense_variant	Exon 2 of 7		XP_011512750.1	O95865V9HW53

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDAH2	ENST00000375789.7 link	c.11C>G	p.Pro4Arg	missense_variant	Exon 1 of 6	2	NM_001303007.2	ENSP00000364945.2		O95865

Frequencies

GnomAD3 genomes

AF:

0.0118

AC:

1785

AN:

151402

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0400

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00631

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.0149

GnomAD2 exomes

AF:

0.00290

AC:

697

AN:

240460

AF XY:

0.00224

show subpopulations

Gnomad AFR exome

AF:

0.0397

Gnomad AMR exome

AF:

0.00299

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000121

Gnomad OTH exome

AF:

0.00101

GnomAD4 exome

AF:

0.00119

AC:

1727

AN:

1454488

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

761

AN XY:

722850

show subpopulations

African (AFR)

AF:

0.0392

AC:

1307

AN:

33352

American (AMR)

AF:

0.00333

AC:

148

AN:

44492

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25846

East Asian (EAS)

AF:

0.00

AC:

AN:

39558

South Asian (SAS)

AF:

0.000326

AC:

AN:

86006

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51948

Middle Eastern (MID)

AF:

0.00244

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.0000515

AC:

AN:

1107402

Other (OTH)

AF:

0.00288

AC:

173

AN:

60142

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

170

255

340

425

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0118

AC:

1795

AN:

151522

Hom.:

Cov.:

AF XY:

0.0110

AC XY:

813

AN XY:

74038

show subpopulations

African (AFR)

AF:

0.0401

AC:

1656

AN:

41308

American (AMR)

AF:

0.00630

AC:

AN:

15230

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5102

South Asian (SAS)

AF:

0.000209

AC:

AN:

4780

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10552

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

67776

Other (OTH)

AF:

0.0148

AC:

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

159

238

318

397

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00379

Hom.:

Bravo

AF:

0.0136

ESP6500AA

AF:

0.0395

AC:

118

ESP6500EA

AF:

0.000186

AC:

ExAC

AF:

0.00339

AC:

397

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 24, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0086

T;T;T;T;.

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.91

MetaRNN

Benign

0.0043

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;L;L;.;.

PhyloP100

3.0

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.36

N;N;N;N;N

REVEL

Benign

0.11

Sift

Pathogenic

0.0

D;D;D;D;D

Sift4G

Benign

0.36

T;T;T;.;T

Polyphen

1.0

D;D;D;.;.

Vest4

0.39

MVP

0.093

MPC

1.0

ClinPred

0.042

GERP RS

5.1

PromoterAI

0.024

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.19

gMVP

0.45

Mutation Taster

=100/0

polymorphism

(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

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6-31729151-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over