6-31729610-C-T

Variant names:

• chr6-31729610-C-T
• rs805305
• ENST00000375792.7:c.-64-385G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_013974.3(DDAH2):​c.-64-385G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DDAH2 NM_013974.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.795
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013974.3. 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
	DDAH2	NM_013974.3		c.-64-385G>A		intron	N/A	NP_039268.1	O95865
	DDAH2	NM_001303008.2		c.-313G>A		upstream_gene	N/A	NP_001289937.1	O95865

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDAH2	ENST00000375792.7	TSL:1	c.-64-385G>A		intron	N/A	ENSP00000364949.3	O95865
	DDAH2	ENST00000921344.1		c.-449G>A		5_prime_UTR	Exon 1 of 6	ENSP00000591403.1
	DDAH2	ENST00000970328.1		c.-449G>A		5_prime_UTR	Exon 1 of 5	ENSP00000640387.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 34392 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 17866

African (AFR) AF: 0.00 AC: 0 AN: 976

American (AMR) AF: 0.00 AC: 0 AN: 3142

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 990

East Asian (EAS) AF: 0.00 AC: 0 AN: 1636

South Asian (SAS) AF: 0.00 AC: 0 AN: 3052

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1456

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 138

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 21050

Other (OTH) AF: 0.00 AC: 0 AN: 1952

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.7
DANN	Benign	0.88
PhyloP100		0.80
PromoterAI		0.14	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs805305; hg19: chr6-31697387;