10-74176904-G-C

Variant names:

• chr10-74176904-G-C
• rs1002041671
• NM_006721.4:c.66-23860G>C

Variant summary

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

The NM_006721.4(ADK):​c.66-23860G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,604 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 6.9e-7 (0 hom.)
• Consequence: ADK NM_006721.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47
• 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: 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=-0.78).

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.66-23860G>C		intron	N/A	NP_006712.2
	ADK	NM_001123.4		c.14+18G>C		intron	N/A	NP_001114.2
	ADK	NM_001202449.2		c.14+18G>C		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.66-23860G>C		intron	N/A	ENSP00000443965.2	P55263-1
	ADK	ENST00000286621.7	TSL:1	c.66-23860G>C		intron	N/A	ENSP00000286621.3	A0A5K1VW54
	ADK	ENST00000372734.5	TSL:1	c.14+18G>C		intron	N/A	ENSP00000361819.3	P55263-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457604 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 725306

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26076

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86088

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49714

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111792

Other (OTH) AF: 0.00 AC: 0 AN: 60338

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.8
DANN	Benign	0.59
PhyloP100		1.5
PromoterAI		0.0073	Neutral

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

Other links and lift over

dbSNP: rs1002041671; hg19: chr10-75936662;