7-140673740-C-T

Variant names:

• chr7-140673740-C-T
• rs61737092
• NM_052853.4:c.410C>T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_052853.4(ADCK2):​c.410C>T​(p.Ala137Val) variant causes a missense change. The variant allele was found at a frequency of 0.00366 in 1,612,986 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0024 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0038 (19 hom.)
• Consequence: ADCK2 NM_052853.4 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 5.28

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 Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008479744).
• BP6: Variant 7-140673740-C-T is Benign according to our data. Variant chr7-140673740-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3053008.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCK2	NM_052853.4	c.410C>T	p.Ala137Val	missense_variant	Exon 1 of 8	ENST00000072869.9	NP_443085.2
ADCK2	XM_011516675.4	c.410C>T	p.Ala137Val	missense_variant	Exon 1 of 7		XP_011514977.1
ADCK2	XM_006716170.5	c.410C>T	p.Ala137Val	missense_variant	Exon 1 of 7		XP_006716233.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCK2	ENST00000072869.9	c.410C>T	p.Ala137Val	missense_variant	Exon 1 of 8	1	NM_052853.4	ENSP00000072869.4
ADCK2	ENST00000476491.5	c.410C>T	p.Ala137Val	missense_variant	Exon 1 of 8	1		ENSP00000420512.1
DENND2A	ENST00000489552.1	c.-146+134G>A		intron_variant	Intron 1 of 1	4		ENSP00000418088.1
ADCK2	ENST00000483369.5	c.-80C>T		upstream_gene_variant		5		ENSP00000417367.1

Frequencies

GnomAD3 genomes AF: 0.00239 AC: 364 AN: 152112 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000772

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00406

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00169

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00359

Gnomad OTH AF: 0.00334

GnomAD3 exomes AF: 0.00210 AC: 525 AN: 250482 Hom.: 3 AF XY: 0.00205 AC XY: 277 AN XY: 135418

Gnomad AFR exome AF: 0.000554

Gnomad AMR exome AF: 0.00202

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000901

Gnomad NFE exome AF: 0.00368

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00379 AC: 5536 AN: 1460756 Hom.: 19 Cov.: 32 AF XY: 0.00371 AC XY: 2697 AN XY: 726718

Gnomad4 AFR exome AF: 0.000538

Gnomad4 AMR exome AF: 0.00212

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00103

Gnomad4 NFE exome AF: 0.00462

Gnomad4 OTH exome AF: 0.00361

GnomAD4 genome AF: 0.00239 AC: 364 AN: 152230 Hom.: 0 Cov.: 32 AF XY: 0.00216 AC XY: 161 AN XY: 74424

Gnomad4 AFR AF: 0.000770

Gnomad4 AMR AF: 0.00405

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00169

Gnomad4 NFE AF: 0.00359

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00323 Hom.: 4

Bravo AF: 0.00244

TwinsUK AF: 0.00458 AC: 17

ALSPAC AF: 0.00363 AC: 14

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00337 AC: 29

ExAC AF: 0.00194 AC: 235

EpiCase AF: 0.00463

EpiControl AF: 0.00403

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

ADCK2-related disorder Benign:1

Apr 20, 2023

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.017	T;.
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.0085	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-2.2	N;N
REVEL	Benign	0.11
Sift	Benign	0.12	T;T
Sift4G	Benign	0.14	T;T
Polyphen		0.85	P;P
Vest4		0.19
MVP		0.31
MPC		0.84
ClinPred		0.029	T
GERP RS		4.6
Varity_R		0.25
gMVP		0.60

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

LitVar

Other links and lift over

dbSNP: rs61737092; hg19: chr7-140373540;