chr6-31730311-T-G

Position:

• chr6-31730311-T-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.68).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDAH2	NM_013974.3			upstream_gene_variant			NP_039268.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDAH2	ENST00000375792.7	c.-325A>C		5_prime_UTR_variant	1/7	1		ENSP00000364949	P1
DDAH2	ENST00000375787.6			upstream_gene_variant		5		ENSP00000364943	P1
DDAH2	ENST00000483792.1			upstream_gene_variant		5

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

Gnomad4 AFR exome AF: 0.705

Gnomad4 AMR exome AF: 0.383

Gnomad4 ASJ exome AF: 0.315

Gnomad4 EAS exome AF: 0.345

Gnomad4 SAS exome AF: 0.396

Gnomad4 FIN exome AF: 0.441

Gnomad4 NFE exome AF: 0.313

Gnomad4 OTH exome AF: 0.388

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

Gnomad4 AFR AF: 0.706

Gnomad4 AMR AF: 0.442

Gnomad4 ASJ AF: 0.341

Gnomad4 EAS AF: 0.401

Gnomad4 SAS AF: 0.446

Gnomad4 FIN AF: 0.485

Gnomad4 NFE AF: 0.359

Gnomad4 OTH AF: 0.473

Alfa AF: 0.387 Hom.: 6785

Bravo AF: 0.483

Asia WGS AF: 0.520 AC: 1805 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	4.8
DANN	Benign	0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs805304; hg19: chr6-31698088;