12-56248119-G-A

Position:

• chr12-56248119-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The ENST00000267116.8(ANKRD52):​c.1882C>T​(p.Arg628Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,386 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: ANKRD52 ENST00000267116.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.825

Genes affected

ANKRD52 (HGNC:26614): (ankyrin repeat domain 52)

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD52	NM_173595.4	c.1882C>T	p.Arg628Cys	missense_variant	18/28	ENST00000267116.8	NP_775866.2
ANKRD52	XM_017019183.2	c.1879C>T	p.Arg627Cys	missense_variant	17/27		XP_016874672.1
ANKRD52	XM_011538197.3	c.1699C>T	p.Arg567Cys	missense_variant	17/27		XP_011536499.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD52	ENST00000267116.8	c.1882C>T	p.Arg628Cys	missense_variant	18/28	1	NM_173595.4	ENSP00000267116	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000804 AC: 2 AN: 248736 Hom.: 0 AF XY: 0.0000148 AC XY: 2 AN XY: 135102

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000887

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461386 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 726986

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000826 AC: 1

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.1882C>T (p.R628C) alteration is located in exon 18 (coding exon 18) of the ANKRD52 gene. This alteration results from a C to T substitution at nucleotide position 1882, causing the arginine (R) at amino acid position 628 to be replaced by a cysteine (C). 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	Uncertain	0.43
BayesDel_addAF	Uncertain	0.023	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Benign	0.067
Eigen_PC	Benign	0.025
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.074	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	1.3	L
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Uncertain	0.42
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.61
MutPred		0.62		Gain of catalytic residue at T631 (P = 0.0017);
MVP		0.73
MPC		2.2
ClinPred		0.99	D
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.59
gMVP		0.74

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: rs777085738; hg19: chr12-56641903;