6-31728636-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.786

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]

ACMG classification

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 GnomAd at 933 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDAH2	NM_001303007.2	c.397+10G>C		intron_variant		ENST00000375789.7
DDAH2	NM_001303008.2	c.397+10G>C		intron_variant
DDAH2	NM_013974.3	c.397+10G>C		intron_variant
DDAH2	XM_011514448.3	c.397+10G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDAH2	ENST00000375789.7	c.397+10G>C		intron_variant		2	NM_001303007.2	P1

Frequencies

GnomAD3 genomes AF: 0.00613 AC: 933 AN: 152150 Hom.: 6 Cov.: 32

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.: 24 AF XY: 0.00843 AC XY: 1132 AN XY: 134214

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.: 33 AF XY: 0.00641 AC XY: 4661 AN XY: 726616

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.: 7 Cov.: 32 AF XY: 0.00672 AC XY: 500 AN XY: 74458

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.: 3

Bravo AF: 0.00652

Asia WGS AF: 0.0160 AC: 57 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

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

Other links and lift over

dbSNP: rs11752493; hg19: chr6-31696413;