6-31730575-T-C

Variant names:

• chr6-31730575-T-C
• rs2272592
• ENST00000375792.7:c.-589A>G

Variant summary

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

The ENST00000375792.7(DDAH2):​c.-589A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.861 in 484,664 control chromosomes in the GnomAD database, including 180,895 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 0.88 (59013 hom., cov: 32)
  • Exomes 𝑓: 0.85 (121882 hom.)
• Consequence: DDAH2 ENST00000375792.7 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.62
• Publications: 26 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]

CLIC1 (HGNC:2062): (chloride intracellular channel 1) Chloride channels are a diverse group of proteins that regulate fundamental cellular processes including stabilization of cell membrane potential, transepithelial transport, maintenance of intracellular pH, and regulation of cell volume. Chloride intracellular channel 1 is a member of the p64 family; the protein localizes principally to the cell nucleus and exhibits both nuclear and plasma membrane chloride ion channel activity. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.959 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLIC1	NM_001288.6	MANE Select	c.*267A>G		downstream_gene	N/A	NP_001279.2
	CLIC1	NM_001287593.1		c.*267A>G		downstream_gene	N/A	NP_001274522.1	O00299
	CLIC1	NM_001287594.3		c.*267A>G		downstream_gene	N/A	NP_001274523.1	O00299

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDAH2	ENST00000375792.7	TSL:1	c.-589A>G		5_prime_UTR	Exon 1 of 7	ENSP00000364949.3	O95865
	CLIC1	ENST00000375784.8	TSL:1 MANE Select	c.*267A>G		downstream_gene	N/A	ENSP00000364940.3	O00299
	CLIC1	ENST00000375780.6	TSL:1	c.*267A>G		downstream_gene	N/A	ENSP00000364935.2	O00299

Frequencies

GnomAD3 genomes AF: 0.878 AC: 133535 AN: 152092 Hom.: 58952 Cov.: 32

Gnomad AFR AF: 0.967

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.914

Gnomad ASJ AF: 0.935

Gnomad EAS AF: 0.785

Gnomad SAS AF: 0.894

Gnomad FIN AF: 0.845

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.824

Gnomad OTH AF: 0.904

GnomAD4 exome AF: 0.854 AC: 283862 AN: 332454 Hom.: 121882 Cov.: 3 AF XY: 0.857 AC XY: 148428 AN XY: 173158

African (AFR) AF: 0.967 AC: 9718 AN: 10048

American (AMR) AF: 0.922 AC: 11876 AN: 12880

Ashkenazi Jewish (ASJ) AF: 0.933 AC: 10328 AN: 11070

East Asian (EAS) AF: 0.874 AC: 20910 AN: 23920

South Asian (SAS) AF: 0.904 AC: 25915 AN: 28656

European-Finnish (FIN) AF: 0.838 AC: 18267 AN: 21798

Middle Eastern (MID) AF: 0.926 AC: 1439 AN: 1554

European-Non Finnish (NFE) AF: 0.831 AC: 167903 AN: 202160

Other (OTH) AF: 0.859 AC: 17506 AN: 20368

GnomAD4 genome AF: 0.878 AC: 133656 AN: 152210 Hom.: 59013 Cov.: 32 AF XY: 0.879 AC XY: 65390 AN XY: 74424

African (AFR) AF: 0.967 AC: 40184 AN: 41544

American (AMR) AF: 0.914 AC: 13974 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.935 AC: 3243 AN: 3470

East Asian (EAS) AF: 0.785 AC: 4058 AN: 5168

South Asian (SAS) AF: 0.895 AC: 4320 AN: 4828

European-Finnish (FIN) AF: 0.845 AC: 8954 AN: 10596

Middle Eastern (MID) AF: 0.942 AC: 277 AN: 294

European-Non Finnish (NFE) AF: 0.824 AC: 56036 AN: 67996

Other (OTH) AF: 0.903 AC: 1907 AN: 2112

Alfa AF: 0.851 Hom.: 108206

Bravo AF: 0.887

Asia WGS AF: 0.897 AC: 3121 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.12
DANN	Benign	0.63
PhyloP100		-3.6
PromoterAI		-0.028	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: rs2272592; hg19: chr6-31698352;