ENST00000375792.7:c.-194G>C

Variant names:

• chr6-31730180-C-G
• rs9267551
• ENST00000375792.7:c.-194G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 23 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=-0.75).
• 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 rank	MANE	Protein	UniProt
DDAH2	NM_013974.3	c.-194G>C		5_prime_UTR_variant	Exon 1 of 7		NP_039268.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDAH2	ENST00000375792.7	c.-194G>C		5_prime_UTR_variant	Exon 1 of 7	1		ENSP00000364949.3
DDAH2	ENST00000480913.5	n.48G>C		non_coding_transcript_exon_variant	Exon 1 of 6	5
DDAH2	ENST00000483792.1	n.83G>C		non_coding_transcript_exon_variant	Exon 1 of 5	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

African (AFR) AF: 1.00 AC: 26 AN: 26

American (AMR) AF: 0.938 AC: 15 AN: 16

Ashkenazi Jewish (ASJ) AF: 0.969 AC: 31 AN: 32

East Asian (EAS) AF: 1.00 AC: 94 AN: 94

South Asian (SAS) AF: 1.00 AC: 14 AN: 14

European-Finnish (FIN) AF: 0.847 AC: 61 AN: 72

Middle Eastern (MID) AF: 1.00 AC: 10 AN: 10

European-Non Finnish (NFE) AF: 0.852 AC: 554 AN: 650

Other (OTH) AF: 0.875 AC: 28 AN: 32

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

African (AFR) AF: 0.975 AC: 40560 AN: 41582

American (AMR) AF: 0.937 AC: 14336 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.968 AC: 3362 AN: 3472

East Asian (EAS) AF: 0.995 AC: 5156 AN: 5180

South Asian (SAS) AF: 0.974 AC: 4701 AN: 4828

European-Finnish (FIN) AF: 0.875 AC: 9281 AN: 10610

Middle Eastern (MID) AF: 0.963 AC: 283 AN: 294

European-Non Finnish (NFE) AF: 0.863 AC: 58682 AN: 68008

Other (OTH) AF: 0.940 AC: 1985 AN: 2112

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
PhyloP100		0.22
PromoterAI		-0.16	Neutral
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: rs9267551; hg19: chr6-31697957;