6-31730180-C-G

Position:

• chr6-31730180-C-G

Variant summary

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

The ENST00000375792.7(DDAH2):​c.-194G>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 0.914 in 153,246 control chromosomes in the GnomAD database, including 64,197 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 0.91 (63826 hom., cov: 32)
  • Exomes 𝑓: 0.88 (371 hom.)
• Consequence: DDAH2 ENST00000375792.7 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.223

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=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDAH2	NM_013974.3	c.-194G>C		5_prime_UTR_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDAH2	ENST00000375792.7	c.-194G>C		5_prime_UTR_variant	1/7	1		P1
DDAH2	ENST00000375787.6	c.-190G>C		5_prime_UTR_variant	1/7	5		P1
DDAH2	ENST00000480913.5	n.48G>C		non_coding_transcript_exon_variant	1/6	5

Frequencies

GnomAD3 genomes AF: 0.914 AC: 139071 AN: 152182 Hom.: 63760 Cov.: 32

Gnomad AFR AF: 0.975

Gnomad AMI AF: 0.931

Gnomad AMR AF: 0.937

Gnomad ASJ AF: 0.968

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.974

Gnomad FIN AF: 0.875

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.863

Gnomad OTH AF: 0.939

GnomAD4 exome AF: 0.881 AC: 833 AN: 946 Hom.: 371 Cov.: 0 AF XY: 0.887 AC XY: 463 AN XY: 522

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.938

Gnomad4 ASJ exome AF: 0.969

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.847

Gnomad4 NFE exome AF: 0.852

Gnomad4 OTH exome AF: 0.875

GnomAD4 genome AF: 0.914 AC: 139195 AN: 152300 Hom.: 63826 Cov.: 32 AF XY: 0.916 AC XY: 68169 AN XY: 74458

Gnomad4 AFR AF: 0.975

Gnomad4 AMR AF: 0.937

Gnomad4 ASJ AF: 0.968

Gnomad4 EAS AF: 0.995

Gnomad4 SAS AF: 0.974

Gnomad4 FIN AF: 0.875

Gnomad4 NFE AF: 0.863

Gnomad4 OTH AF: 0.940

Alfa AF: 0.803 Hom.: 1708

Bravo AF: 0.922

Asia WGS AF: 0.980 AC: 3409 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.3
DANN	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9267551; hg19: chr6-31697957;