2-70982001-A-C

Position:

• chr2-70982001-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001115116.2(ANKRD53):​c.683A>C​(p.Lys228Thr) 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: ANKRD53 NM_001115116.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.30

Genes affected

ANKRD53 (HGNC:25691): (ankyrin repeat domain 53) Involved in mitotic metaphase plate congression; regulation of microtubule cytoskeleton organization; and regulation of mitotic cytokinesis. Located in spindle pole. [provided by Alliance of Genome Resources, Apr 2022]

LOC105374795 (HGNC:):

TEX261 (HGNC:30712): (testis expressed 261) Predicted to enable COPII receptor activity. Predicted to be involved in endoplasmic reticulum to Golgi vesicle-mediated transport. Predicted to act upstream of or within positive regulation of apoptotic process. Predicted to be located in cytoplasm. Predicted to be integral component of membrane. Predicted to be active in COPII-coated ER to Golgi transport vesicle. Predicted to be integral component of Golgi membrane and integral component of endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4071403).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD53	NM_001115116.2	c.683A>C	p.Lys228Thr	missense_variant	4/6	ENST00000360589.4
LOC105374795	XR_001739534.2	n.439+1692T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD53	ENST00000360589.4	c.683A>C	p.Lys228Thr	missense_variant	4/6	2	NM_001115116.2	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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 06, 2021

The c.683A>C (p.K228T) alteration is located in exon 4 (coding exon 4) of the ANKRD53 gene. This alteration results from a A to C substitution at nucleotide position 683, causing the lysine (K) at amino acid position 228 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	Uncertain	0.44
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	23
DANN	Uncertain	1.0
Eigen	Benign	0.0032
Eigen_PC	Benign	-0.037
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.66	T;T;T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.41	T;T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.3	L;.;L
MutationTaster	Benign	0.85	N;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-2.1	N;N;N
REVEL	Benign	0.24
Sift	Benign	0.053	T;D;D
Sift4G	Uncertain	0.028	D;D;D
Polyphen		0.89	P;.;P
Vest4		0.35
MutPred		0.62		Loss of ubiquitination at K228 (P = 0.0412);.;Loss of ubiquitination at K228 (P = 0.0412);
MVP		0.79
MPC		0.94
ClinPred		0.81	D
GERP RS		2.9
Varity_R		0.20
gMVP		0.43

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: chr2-71209131;