rs12252558

Variant names:

• chr10-74200688-A-T
• rs12252558
• NM_006721.4:c.66-76A>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006721.4(ADK):​c.66-76A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0125 in 967,422 control chromosomes in the GnomAD database, including 990 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.049 (649 hom., cov: 32)
  • Exomes 𝑓: 0.0057 (341 hom.)
• Consequence: ADK NM_006721.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.22
• Publications: 0 publications found

Genes affected

ADK (HGNC:257): (adenosine kinase) This gene an enzyme which catalyzes the transfer of the gamma-phosphate from ATP to adenosine, thereby serving as a regulator of concentrations of both extracellular adenosine and intracellular adenine nucleotides. Adenosine has widespread effects on the cardiovascular, nervous, respiratory, and immune systems and inhibitors of the enzyme could play an important pharmacological role in increasing intravascular adenosine concentrations and acting as anti-inflammatory agents. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2011]

ADK Gene-Disease associations (from GenCC):

• adenosine kinase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 10-74200688-A-T is Benign according to our data. Variant chr10-74200688-A-T is described in ClinVar as Benign. ClinVar VariationId is 1249834.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006721.4. 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
	ADK	NM_006721.4	MANE Select	c.66-76A>T		intron	N/A	NP_006712.2
	ADK	NM_001123.4		c.15-76A>T		intron	N/A	NP_001114.2
	ADK	NM_001202449.2		c.15-76A>T		intron	N/A	NP_001189378.1	P55263-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADK	ENST00000539909.6	TSL:2 MANE Select	c.66-76A>T		intron	N/A	ENSP00000443965.2	P55263-1
	ADK	ENST00000286621.7	TSL:1	c.66-76A>T		intron	N/A	ENSP00000286621.3	A0A5K1VW54
	ADK	ENST00000372734.5	TSL:1	c.15-76A>T		intron	N/A	ENSP00000361819.3	P55263-2

Frequencies

GnomAD3 genomes AF: 0.0494 AC: 7505 AN: 152028 Hom.: 644 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0194

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000573

Gnomad OTH AF: 0.0325

GnomAD4 exome AF: 0.00566 AC: 4612 AN: 815276 Hom.: 341 AF XY: 0.00454 AC XY: 1940 AN XY: 427004

African (AFR) AF: 0.176 AC: 3576 AN: 20374

American (AMR) AF: 0.00919 AC: 336 AN: 36578

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21744

East Asian (EAS) AF: 0.00 AC: 0 AN: 34388

South Asian (SAS) AF: 0.000479 AC: 33 AN: 68944

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46458

Middle Eastern (MID) AF: 0.00984 AC: 37 AN: 3760

European-Non Finnish (NFE) AF: 0.000290 AC: 158 AN: 544330

Other (OTH) AF: 0.0122 AC: 472 AN: 38700

GnomAD4 genome AF: 0.0495 AC: 7525 AN: 152146 Hom.: 649 Cov.: 32 AF XY: 0.0467 AC XY: 3471 AN XY: 74382

African (AFR) AF: 0.172 AC: 7115 AN: 41478

American (AMR) AF: 0.0194 AC: 296 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000574 AC: 39 AN: 68000

Other (OTH) AF: 0.0321 AC: 68 AN: 2116

Alfa AF: 0.0377 Hom.: 55

Bravo AF: 0.0570

Asia WGS AF: 0.00866 AC: 30 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Benign	0.68
PhyloP100		2.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs12252558; hg19: chr10-75960446;