6-31729151-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001303007.2(DDAH2):c.11C>G(p.Pro4Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00219 in 1,606,010 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (28 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (24 hom.)
• Consequence: DDAH2 NM_001303007.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.04

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0043207705).
• BP6: Variant 6-31729151-G-C is Benign according to our data. Variant chr6-31729151-G-C is described in ClinVar as [Benign]. Clinvar id is 786084.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0118 (1795/151522) while in subpopulation AFR AF= 0.0401 (1656/41308). AF 95% confidence interval is 0.0385. There are 28 homozygotes in gnomad4. There are 813 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 1785 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDAH2	NM_001303007.2	c.11C>G	p.Pro4Arg	missense_variant	1/6	ENST00000375789.7
DDAH2	NM_001303008.2	c.11C>G	p.Pro4Arg	missense_variant	2/7
DDAH2	NM_013974.3	c.11C>G	p.Pro4Arg	missense_variant	2/7
DDAH2	XM_011514448.3	c.11C>G	p.Pro4Arg	missense_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDAH2	ENST00000375789.7	c.11C>G	p.Pro4Arg	missense_variant	1/6	2	NM_001303007.2	P1

Frequencies

GnomAD3 genomes AF: 0.0118 AC: 1785 AN: 151402 Hom.: 28 Cov.: 32

Gnomad AFR AF: 0.0400

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00631

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0149

GnomAD3 exomes AF: 0.00290 AC: 697 AN: 240460 Hom.: 8 AF XY: 0.00224 AC XY: 296 AN XY: 131868

Gnomad AFR exome AF: 0.0397

Gnomad AMR exome AF: 0.00299

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000333

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000121

Gnomad OTH exome AF: 0.00101

GnomAD4 exome AF: 0.00119 AC: 1727 AN: 1454488 Hom.: 24 Cov.: 32 AF XY: 0.00105 AC XY: 761 AN XY: 722850

Gnomad4 AFR exome AF: 0.0392

Gnomad4 AMR exome AF: 0.00333

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000326

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000515

Gnomad4 OTH exome AF: 0.00288

GnomAD4 genome AF: 0.0118 AC: 1795 AN: 151522 Hom.: 28 Cov.: 32 AF XY: 0.0110 AC XY: 813 AN XY: 74038

Gnomad4 AFR AF: 0.0401

Gnomad4 AMR AF: 0.00630

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000209

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.0148

Alfa AF: 0.00379 Hom.: 1

Bravo AF: 0.0136

ESP6500AA AF: 0.0395 AC: 118

ESP6500EA AF: 0.000186 AC: 1

ExAC AF: 0.00339 AC: 397

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.35
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.0086	T;T;T;T;.
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.91	D
MetaRNN	Benign	0.0043	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L;L;.;.
MutationTaster	Benign	0.64	D;D;D
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.36	N;N;N;N;N
REVEL	Benign	0.11
Sift	Pathogenic	0.0	D;D;D;D;D
Sift4G	Benign	0.36	T;T;T;.;T
Polyphen		1.0	D;D;D;.;.
Vest4		0.39
MVP		0.093
MPC		1.0
ClinPred		0.042	T
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.19
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs73728976; hg19: chr6-31696928; COSMIC: COSV99058878; COSMIC: COSV99058878;