7-140674024-C-T

Position:

• chr7-140674024-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_052853.4(ADCK2):​c.694C>T​(p.Leu232Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADCK2 NM_052853.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.24

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1448155).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADCK2	NM_052853.4	c.694C>T	p.Leu232Phe	missense_variant	1/8	ENST00000072869.9	NP_443085.2
ADCK2	XM_011516675.4	c.694C>T	p.Leu232Phe	missense_variant	1/7		XP_011514977.1
ADCK2	XM_006716170.5	c.694C>T	p.Leu232Phe	missense_variant	1/7		XP_006716233.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADCK2	ENST00000072869.9	c.694C>T	p.Leu232Phe	missense_variant	1/8	1	NM_052853.4	ENSP00000072869.4
ADCK2	ENST00000476491.5	c.694C>T	p.Leu232Phe	missense_variant	1/8	1		ENSP00000420512.1
ADCK2	ENST00000483369.5	c.205C>T	p.Leu69Phe	missense_variant	1/8	5		ENSP00000417367.1
DENND2A	ENST00000489552.1	c.-296G>A		upstream_gene_variant		4		ENSP00000418088.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 12, 2022

The c.694C>T (p.L232F) alteration is located in exon 1 (coding exon 1) of the ADCK2 gene. This alteration results from a C to T substitution at nucleotide position 694, causing the leucine (L) at amino acid position 232 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0074	T;.
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	2.0	M;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.091
Sift	Benign	0.052	T;D
Sift4G	Uncertain	0.060	T;D
Polyphen		0.32	B;P
Vest4		0.13
MutPred		0.56		Loss of sheet (P = 0.0483);Loss of sheet (P = 0.0483);
MVP		0.26
MPC		1.1
ClinPred		0.86	D
GERP RS		3.7
Varity_R		0.054
gMVP		0.42

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-140373824;