6-31728636-C-G

Variant names:

• chr6-31728636-C-G
• rs11752493
• NM_001303007.2:c.397+10G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001303007.2(DDAH2):​c.397+10G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.006 in 1,612,868 control chromosomes in the GnomAD database, including 138 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0062 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0060 (131 hom.)
• Consequence: DDAH2 NM_001303007.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.786
• Publications: 3 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 6-31728636-C-G is Benign according to our data. Variant chr6-31728636-C-G is described in ClinVar as [Benign]. Clinvar id is 783629.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.00598 (8729/1460600) while in subpopulation EAS AF = 0.0443 (1760/39696). AF 95% confidence interval is 0.0426. There are 131 homozygotes in GnomAdExome4. There are 4661 alleles in the male GnomAdExome4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 943 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDAH2	NM_001303007.2	c.397+10G>C		intron_variant	Intron 2 of 5	ENST00000375789.7	NP_001289936.1
DDAH2	NM_001303008.2	c.397+10G>C		intron_variant	Intron 3 of 6		NP_001289937.1
DDAH2	NM_013974.3	c.397+10G>C		intron_variant	Intron 3 of 6		NP_039268.1
DDAH2	XM_011514448.3	c.397+10G>C		intron_variant	Intron 3 of 6		XP_011512750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDAH2	ENST00000375789.7	c.397+10G>C		intron_variant	Intron 2 of 5	2	NM_001303007.2	ENSP00000364945.2

Frequencies

GnomAD3 genomes AF: 0.00613 AC: 933 AN: 152150 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00403

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00746

Gnomad ASJ AF: 0.0372

Gnomad EAS AF: 0.0150

Gnomad SAS AF: 0.0134

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00509

Gnomad OTH AF: 0.0105

GnomAD2 exomes AF: 0.00762 AC: 1877 AN: 246192 AF XY: 0.00843

Gnomad AFR exome AF: 0.00338

Gnomad AMR exome AF: 0.00497

Gnomad ASJ exome AF: 0.0398

Gnomad EAS exome AF: 0.0130

Gnomad FIN exome AF: 0.000463

Gnomad NFE exome AF: 0.00510

Gnomad OTH exome AF: 0.0119

GnomAD4 exome AF: 0.00598 AC: 8729 AN: 1460600 Hom.: 131 Cov.: 33 AF XY: 0.00641 AC XY: 4661 AN XY: 726616

African (AFR) AF: 0.00573 AC: 192 AN: 33480

American (AMR) AF: 0.00539 AC: 241 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.0412 AC: 1076 AN: 26130

East Asian (EAS) AF: 0.0443 AC: 1760 AN: 39696

South Asian (SAS) AF: 0.0123 AC: 1061 AN: 86244

European-Finnish (FIN) AF: 0.000669 AC: 35 AN: 52306

Middle Eastern (MID) AF: 0.0267 AC: 154 AN: 5768

European-Non Finnish (NFE) AF: 0.00331 AC: 3678 AN: 1111892

Other (OTH) AF: 0.00881 AC: 532 AN: 60378

GnomAD4 genome AF: 0.00619 AC: 943 AN: 152268 Hom.: 7 Cov.: 32 AF XY: 0.00672 AC XY: 500 AN XY: 74458

African (AFR) AF: 0.00426 AC: 177 AN: 41538

American (AMR) AF: 0.00745 AC: 114 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0372 AC: 129 AN: 3468

East Asian (EAS) AF: 0.0150 AC: 78 AN: 5184

South Asian (SAS) AF: 0.0135 AC: 65 AN: 4830

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10620

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00509 AC: 346 AN: 68012

Other (OTH) AF: 0.0104 AC: 22 AN: 2116

Alfa AF: 0.00870 Hom.: 3

Bravo AF: 0.00652

Asia WGS AF: 0.0160 AC: 57 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 01, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.29
DANN	Benign	0.53
PhyloP100		-0.79
PromoterAI		-0.11	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism

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: rs11752493; hg19: chr6-31696413;