Variant 6-31727289-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001303007.2(DDAH2):c.806G>T(p.Gly269Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

DDAH2
NM_001303007.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.83

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:

DDAH2 (HGNC:):

DDAH2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.838

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDAH2	NM_001303007.2 linkuse as main transcript	c.806G>T	p.Gly269Val	missense_variant	6/6	ENST00000375789.7	NP_001289936.1	O95865V9HW53
DDAH2	NM_001303008.2 linkuse as main transcript	c.806G>T	p.Gly269Val	missense_variant	7/7		NP_001289937.1	O95865V9HW53
DDAH2	NM_013974.3 linkuse as main transcript	c.806G>T	p.Gly269Val	missense_variant	7/7		NP_039268.1	O95865V9HW53
DDAH2	XM_011514448.3 linkuse as main transcript	c.806G>T	p.Gly269Val	missense_variant	7/7		XP_011512750.1	O95865V9HW53

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDAH2	ENST00000375789.7 linkuse as main transcript	c.806G>T	p.Gly269Val	missense_variant	6/6	2	NM_001303007.2	ENSP00000364945.2		O95865

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 27, 2024

The c.806G>T (p.G269V) alteration is located in exon 7 (coding exon 6) of the DDAH2 gene. This alteration results from a G to T substitution at nucleotide position 806, causing the glycine (G) at amino acid position 269 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.67

BayesDel_addAF

Pathogenic

0.40

BayesDel_noAF

Pathogenic

0.33

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.39

T;T;T

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Uncertain

0.92

M_CAP

Benign

0.052

MetaRNN

Pathogenic

0.84

D;D;D

MetaSVM

Benign

-0.36

MutationAssessor

Uncertain

2.7

M;M;M

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-2.5

N;N;N

REVEL

Benign

0.27

Sift

Uncertain

0.023

D;D;D

Sift4G

Uncertain

0.016

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.86

MutPred

0.61

Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);

MVP

0.66

MPC

2.3

ClinPred

0.99

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.53

gMVP

0.87

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over