rs707916

Positions:

• chr6-31729781-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000375792.7(DDAH2):​c.-65+270C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 153,686 control chromosomes in the GnomAD database, including 19,029 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.48 (18856 hom., cov: 31)
  • Exomes 𝑓: 0.40 (173 hom.)
• Consequence: DDAH2 ENST00000375792.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.307

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDAH2	XM_011514448.3	c.-163C>T		5_prime_UTR_variant	1/7		XP_011512750.1
DDAH2	NM_013974.3	c.-65+270C>T		intron_variant			NP_039268.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDAH2	ENST00000375792.7	c.-65+270C>T		intron_variant		1		ENSP00000364949	P1
DDAH2	ENST00000416410.6	c.-163C>T		5_prime_UTR_variant	1/7	2		ENSP00000397466	P1
DDAH2	ENST00000375787.6	c.-61+270C>T		intron_variant		5		ENSP00000364943	P1

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72214 AN: 151816 Hom.: 18821 Cov.: 31

Gnomad AFR AF: 0.707

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.471

GnomAD4 exome AF: 0.402 AC: 705 AN: 1752 Hom.: 173 Cov.: 0 AF XY: 0.386 AC XY: 371 AN XY: 962

Gnomad4 AFR exome AF: 0.750

Gnomad4 AMR exome AF: 0.507

Gnomad4 ASJ exome AF: 0.200

Gnomad4 EAS exome AF: 0.300

Gnomad4 SAS exome AF: 0.416

Gnomad4 FIN exome AF: 0.438

Gnomad4 NFE exome AF: 0.369

Gnomad4 OTH exome AF: 0.382

GnomAD4 genome AF: 0.476 AC: 72299 AN: 151934 Hom.: 18856 Cov.: 31 AF XY: 0.479 AC XY: 35539 AN XY: 74228

Gnomad4 AFR AF: 0.707

Gnomad4 AMR AF: 0.441

Gnomad4 ASJ AF: 0.341

Gnomad4 EAS AF: 0.399

Gnomad4 SAS AF: 0.445

Gnomad4 FIN AF: 0.487

Gnomad4 NFE AF: 0.359

Gnomad4 OTH AF: 0.474

Alfa AF: 0.386 Hom.: 6350

Bravo AF: 0.483

Asia WGS AF: 0.519 AC: 1802 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	1.9
DANN	Benign	0.88

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

LitVar

Other links and lift over

dbSNP: rs707916; hg19: chr6-31697558;