Variant chr6-31728636-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001303007.2(DDAH2):c.397+10G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.006 in 1,612,868 control chromosomes in the GnomAD database, including 138 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0062 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0060 ( 131 hom. )

Consequence

DDAH2
NM_001303007.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.786

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 6-31728636-C-G is Benign according to our data. Variant chr6-31728636-C-G is described in ClinVar as [Benign]. Clinvar id is 783629.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00598 (8729/1460600) while in subpopulation EAS AF= 0.0443 (1760/39696). AF 95% confidence interval is 0.0426. There are 131 homozygotes in gnomad4_exome. There are 4661 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 943 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
DDAH2	NM_001303007.2 linkuse as main transcript	c.397+10G>C	intron_variant	ENST00000375789.7	NP_001289936.1	O95865V9HW53
DDAH2	NM_001303008.2 linkuse as main transcript	c.397+10G>C	intron_variant		NP_001289937.1	O95865V9HW53
DDAH2	NM_013974.3 linkuse as main transcript	c.397+10G>C	intron_variant		NP_039268.1	O95865V9HW53
DDAH2	XM_011514448.3 linkuse as main transcript	c.397+10G>C	intron_variant		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.397+10G>C		intron_variant		2	NM_001303007.2	ENSP00000364945.2		O95865

Frequencies

GnomAD3 genomes

AF:

0.00613

AC:

933

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00403

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00746

Gnomad ASJ

AF:

0.0372

Gnomad EAS

AF:

0.0150

Gnomad SAS

AF:

0.0134

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00509

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00762

AC:

1877

AN:

246192

Hom.:

AF XY:

0.00843

AC XY:

1132

AN XY:

134214

show subpopulations

Gnomad AFR exome

AF:

0.00338

Gnomad AMR exome

AF:

0.00497

Gnomad ASJ exome

AF:

0.0398

Gnomad EAS exome

AF:

0.0130

Gnomad SAS exome

AF:

0.0124

Gnomad FIN exome

AF:

0.000463

Gnomad NFE exome

AF:

0.00510

Gnomad OTH exome

AF:

0.0119

GnomAD4 exome

AF:

0.00598

AC:

8729

AN:

1460600

Hom.:

131

Cov.:

AF XY:

0.00641

AC XY:

4661

AN XY:

726616

show subpopulations

Gnomad4 AFR exome

AF:

0.00573

Gnomad4 AMR exome

AF:

0.00539

Gnomad4 ASJ exome

AF:

0.0412

Gnomad4 EAS exome

AF:

0.0443

Gnomad4 SAS exome

AF:

0.0123

Gnomad4 FIN exome

AF:

0.000669

Gnomad4 NFE exome

AF:

0.00331

Gnomad4 OTH exome

AF:

0.00881

GnomAD4 genome

AF:

0.00619

AC:

943

AN:

152268

Hom.:

Cov.:

AF XY:

0.00672

AC XY:

500

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00426

Gnomad4 AMR

AF:

0.00745

Gnomad4 ASJ

AF:

0.0372

Gnomad4 EAS

AF:

0.0150

Gnomad4 SAS

AF:

0.0135

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00509

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00870

Hom.:

Bravo

AF:

0.00652

Asia WGS

AF:

0.0160

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 01, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.29

DANN

Benign

0.53

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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