7-140673586-C-T

Variant names:

• chr7-140673586-C-T
• rs367917022
• NM_052853.4:c.256C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_052853.4(ADCK2):​c.256C>T​(p.Arg86*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 1,453,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: ADCK2 NM_052853.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.525
• Publications: 1 publications found

Genes affected

ADCK2 (HGNC:19039): (aarF domain containing kinase 2) Predicted to enable ATP binding activity and protein serine/threonine kinase activity. Predicted to be involved in protein phosphorylation. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

DENND2A (HGNC:22212): (DENN domain containing 2A) Enables guanyl-nucleotide exchange factor activity. Involved in retrograde transport, endosome to Golgi. Located in actin cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052853.4. 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
	ADCK2	NM_052853.4	MANE Select	c.256C>T	p.Arg86*	stop_gained	Exon 1 of 8	NP_443085.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCK2	ENST00000072869.9	TSL:1 MANE Select	c.256C>T	p.Arg86*	stop_gained	Exon 1 of 8	ENSP00000072869.4	Q7Z695
	ADCK2	ENST00000476491.5	TSL:1	c.256C>T	p.Arg86*	stop_gained	Exon 1 of 8	ENSP00000420512.1	C9JE15
	ADCK2	ENST00000926717.1		c.256C>T	p.Arg86*	stop_gained	Exon 1 of 9	ENSP00000596776.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000168 AC: 4 AN: 238260 AF XY: 0.0000307

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000371

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000131 AC: 19 AN: 1453118 Hom.: 0 Cov.: 32 AF XY: 0.0000124 AC XY: 9 AN XY: 723078

African (AFR) AF: 0.00 AC: 0 AN: 33458

American (AMR) AF: 0.00 AC: 0 AN: 44552

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26034

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 86058

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46198

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1111142

Other (OTH) AF: 0.0000166 AC: 1 AN: 60238

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.00000825 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Pathogenic	0.24
CADD	Pathogenic	33
DANN	Uncertain	0.99
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.091	N
PhyloP100		-0.53
Vest4		0.049
GERP RS		-0.42
PromoterAI		-0.13	Neutral
Mutation Taster		=29/171	disease causing (fs/PTC)

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: rs367917022; hg19: chr7-140373386; COSMIC: COSV50783848; COSMIC: COSV50783848;