ENST00000375792.7:c.-64-385G>C

Variant names:

• chr6-31729610-C-G
• rs805305
• ENST00000375792.7:c.-64-385G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 49 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000375792.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDAH2	NM_013974.3		c.-64-385G>C		intron	N/A	NP_039268.1
	DDAH2	NM_001303008.2		c.-313G>C		upstream_gene	N/A	NP_001289937.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDAH2	ENST00000375792.7	TSL:1	c.-64-385G>C		intron	N/A	ENSP00000364949.3
	DDAH2	ENST00000375787.6	TSL:5	c.-60-389G>C		intron	N/A	ENSP00000364943.2
	DDAH2	ENST00000416410.6	TSL:2	c.-65+73G>C		intron	N/A	ENSP00000397466.2

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

African (AFR) AF: 0.698 AC: 673 AN: 964

American (AMR) AF: 0.429 AC: 1342 AN: 3128

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 351 AN: 984

East Asian (EAS) AF: 0.382 AC: 622 AN: 1630

South Asian (SAS) AF: 0.426 AC: 1295 AN: 3038

European-Finnish (FIN) AF: 0.440 AC: 639 AN: 1452

Middle Eastern (MID) AF: 0.382 AC: 52 AN: 136

European-Non Finnish (NFE) AF: 0.347 AC: 7263 AN: 20944

Other (OTH) AF: 0.413 AC: 802 AN: 1940

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

African (AFR) AF: 0.707 AC: 29295 AN: 41446

American (AMR) AF: 0.442 AC: 6744 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 1181 AN: 3466

East Asian (EAS) AF: 0.401 AC: 2069 AN: 5158

South Asian (SAS) AF: 0.446 AC: 2138 AN: 4798

European-Finnish (FIN) AF: 0.484 AC: 5101 AN: 10540

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.359 AC: 24362 AN: 67944

Other (OTH) AF: 0.474 AC: 1000 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.4
DANN	Benign	0.60
PhyloP100		0.80
PromoterAI		-0.013	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs805305; hg19: chr6-31697387;