Genetic Variant DDAH2:p.Val152Met (chr6-31728468-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001303007.2(DDAH2):c.454G>A(p.Val152Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,716 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V152L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DDAH2
NM_001303007.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.21

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDAH2	NM_001303007.2 link	c.454G>A	p.Val152Met	missense_variant	Exon 3 of 6	ENST00000375789.7	NP_001289936.1	O95865V9HW53
DDAH2	NM_001303008.2 link	c.454G>A	p.Val152Met	missense_variant	Exon 4 of 7		NP_001289937.1	O95865V9HW53
DDAH2	NM_013974.3 link	c.454G>A	p.Val152Met	missense_variant	Exon 4 of 7		NP_039268.1	O95865V9HW53
DDAH2	XM_011514448.3 link	c.454G>A	p.Val152Met	missense_variant	Exon 4 of 7		XP_011512750.1	O95865V9HW53

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDAH2	ENST00000375789.7 link	c.454G>A	p.Val152Met	missense_variant	Exon 3 of 6	2	NM_001303007.2	ENSP00000364945.2		O95865

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460716

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726672

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52300

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1112004

Other (OTH)

AF:

0.00

AC:

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.68

BayesDel_addAF

Uncertain

0.071

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.029

T;T;T;T;.

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.89

M_CAP

Benign

0.016

MetaRNN

Uncertain

0.57

D;D;D;D;D

MetaSVM

Benign

-0.74

MutationAssessor

Uncertain

2.2

M;M;M;.;.

PhyloP100

4.2

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.40

N;N;N;N;N

REVEL

Benign

0.16

Sift

Uncertain

0.015

D;D;D;D;D

Sift4G

Uncertain

0.017

D;D;D;.;D

Polyphen

1.0

D;D;D;.;.

Vest4

0.52

MutPred

0.66

Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);

MVP

0.32

MPC

2.0

ClinPred

0.80

GERP RS

5.2

PromoterAI

0.29

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.11

gMVP

0.83

Mutation Taster

=84/16

polymorphism

(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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6-31728468-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over