6-31730311-T-G

Variant names:

• chr6-31730311-T-G
• rs805304
• ENST00000375792.7:c.-325A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000375792.7(DDAH2):​c.-325A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 178,096 control chromosomes in the GnomAD database, including 20,589 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 (18854 hom., cov: 34)
  • Exomes 𝑓: 0.35 (1735 hom.)
• Consequence: DDAH2 ENST00000375792.7 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.601
• 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=-0.68).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.699 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.-325A>C		upstream_gene	N/A	NP_039268.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDAH2	ENST00000375792.7	TSL:1	c.-325A>C		5_prime_UTR	Exon 1 of 7	ENSP00000364949.3
	DDAH2	ENST00000375787.6	TSL:5	c.-321A>C		upstream_gene	N/A	ENSP00000364943.2
	DDAH2	ENST00000480913.5	TSL:5	n.-84A>C		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72273 AN: 152016 Hom.: 18819 Cov.: 34

Gnomad AFR AF: 0.706

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.485

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.470

GnomAD4 exome AF: 0.346 AC: 8993 AN: 25962 Hom.: 1735 Cov.: 0 AF XY: 0.344 AC XY: 4658 AN XY: 13536

African (AFR) AF: 0.705 AC: 420 AN: 596

American (AMR) AF: 0.383 AC: 259 AN: 676

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 236 AN: 750

East Asian (EAS) AF: 0.345 AC: 812 AN: 2352

South Asian (SAS) AF: 0.396 AC: 286 AN: 722

European-Finnish (FIN) AF: 0.441 AC: 1181 AN: 2678

Middle Eastern (MID) AF: 0.326 AC: 47 AN: 144

European-Non Finnish (NFE) AF: 0.313 AC: 5207 AN: 16638

Other (OTH) AF: 0.388 AC: 545 AN: 1406

GnomAD4 genome AF: 0.476 AC: 72358 AN: 152134 Hom.: 18854 Cov.: 34 AF XY: 0.478 AC XY: 35568 AN XY: 74376

African (AFR) AF: 0.706 AC: 29295 AN: 41518

American (AMR) AF: 0.442 AC: 6760 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 1183 AN: 3470

East Asian (EAS) AF: 0.401 AC: 2067 AN: 5158

South Asian (SAS) AF: 0.446 AC: 2154 AN: 4826

European-Finnish (FIN) AF: 0.485 AC: 5134 AN: 10590

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

European-Non Finnish (NFE) AF: 0.359 AC: 24381 AN: 67954

Other (OTH) AF: 0.473 AC: 1000 AN: 2112

Alfa AF: 0.443 Hom.: 21706

Bravo AF: 0.483

Asia WGS AF: 0.520 AC: 1805 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	4.8
DANN	Benign	0.67
PhyloP100		-0.60
PromoterAI		0.0060	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs805304; hg19: chr6-31698088;