rs805305

Positions:

• chr6-31729610-C-G
• chr6-31729610-C-T

Variant summary

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

The ENST00000375792.7(DDAH2):​c.-64-385G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 186,142 control chromosomes in the GnomAD database, including 21,517 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 (18841 hom., cov: 32)
  • Exomes 𝑓: 0.38 (2676 hom.)
• Consequence: DDAH2 ENST00000375792.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.795

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=-0.89).
• 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	NM_013974.3	c.-64-385G>C		intron_variant			NP_039268.1
DDAH2	XM_011514448.3	c.-65+73G>C		intron_variant			XP_011512750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDAH2	ENST00000375792.7	c.-64-385G>C		intron_variant		1		ENSP00000364949	P1
DDAH2	ENST00000375787.6	c.-60-389G>C		intron_variant		5		ENSP00000364943	P1
DDAH2	ENST00000416410.6	c.-65+73G>C		intron_variant		2		ENSP00000397466	P1

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72189 AN: 151808 Hom.: 18806 Cov.: 32

Gnomad AFR AF: 0.707

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.471

GnomAD4 exome AF: 0.381 AC: 13039 AN: 34216 Hom.: 2676 Cov.: 0 AF XY: 0.382 AC XY: 6787 AN XY: 17790

Gnomad4 AFR exome AF: 0.698

Gnomad4 AMR exome AF: 0.429

Gnomad4 ASJ exome AF: 0.357

Gnomad4 EAS exome AF: 0.382

Gnomad4 SAS exome AF: 0.426

Gnomad4 FIN exome AF: 0.440

Gnomad4 NFE exome AF: 0.347

Gnomad4 OTH exome AF: 0.413

GnomAD4 genome AF: 0.476 AC: 72274 AN: 151926 Hom.: 18841 Cov.: 32 AF XY: 0.478 AC XY: 35506 AN XY: 74236

Gnomad4 AFR AF: 0.707

Gnomad4 AMR AF: 0.442

Gnomad4 ASJ AF: 0.341

Gnomad4 EAS AF: 0.401

Gnomad4 SAS AF: 0.446

Gnomad4 FIN AF: 0.484

Gnomad4 NFE AF: 0.359

Gnomad4 OTH AF: 0.474

Alfa AF: 0.414 Hom.: 1893

Bravo AF: 0.483

Asia WGS AF: 0.521 AC: 1807 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.4
DANN	Benign	0.60

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: rs805305; hg19: chr6-31697387;