12-56244718-C-T

Variant names:

• chr12-56244718-C-T
• rs766786981
• NM_173595.4:c.2656G>A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_173595.4(ANKRD52):​c.2656G>A​(p.Ala886Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,461,576 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: ANKRD52 NM_173595.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.392

Genes affected

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

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10529968).
• BS2: High AC in GnomAdExome4 at 20 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD52	NM_173595.4	c.2656G>A	p.Ala886Thr	missense_variant	Exon 24 of 28	ENST00000267116.8	NP_775866.2
ANKRD52	XM_017019183.2	c.2653G>A	p.Ala885Thr	missense_variant	Exon 23 of 27		XP_016874672.1
ANKRD52	XM_011538197.3	c.2473G>A	p.Ala825Thr	missense_variant	Exon 23 of 27		XP_011536499.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD52	ENST00000267116.8	c.2656G>A	p.Ala886Thr	missense_variant	Exon 24 of 28	1	NM_173595.4	ENSP00000267116.7
ANKRD52	ENST00000548241.1	n.10G>A		non_coding_transcript_exon_variant	Exon 1 of 6	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000803 AC: 2 AN: 249054 Hom.: 0 AF XY: 0.0000148 AC XY: 2 AN XY: 135146

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000556

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000137 AC: 20 AN: 1461576 Hom.: 0 Cov.: 33 AF XY: 0.0000179 AC XY: 13 AN XY: 727086

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000171

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2656G>A (p.A886T) alteration is located in exon 24 (coding exon 24) of the ANKRD52 gene. This alteration results from a G to A substitution at nucleotide position 2656, causing the alanine (A) at amino acid position 886 to be replaced by a threonine (T). 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	0.083
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.3	L
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.051
Sift	Benign	0.47	T
Sift4G	Benign	0.71	T
Polyphen		0.067	B
Vest4		0.23
MutPred		0.45		Gain of catalytic residue at A886 (P = 0.0203);
MVP		0.54
MPC		0.84
ClinPred		0.25	T
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.060
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs766786981; hg19: chr12-56638502;