2-96839780-T-G

Position:

• chr2-96839780-T-G

Variant summary

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

The NM_144994.8(ANKRD23):​c.769A>C​(p.Lys257Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ANKRD23 NM_144994.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.17

Genes affected

ANKRD23 (HGNC:24470): (ankyrin repeat domain 23) This gene is a member of the muscle ankyrin repeat protein (MARP) family and encodes a protein with four tandem ankyrin-like repeats. The protein is localized to the nucleus, functioning as a transcriptional regulator. Expression of this protein is induced during recovery following starvation. [provided by RefSeq, Jul 2008]

ANKRD39 (HGNC:28640): (ankyrin repeat domain 39) Predicted to contribute to ubiquitin-protein transferase activity. Predicted to be involved in protein K6-linked ubiquitination. Predicted to be part of BRCA1-A complex and BRCA1-BARD1 complex. [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=0.30527586).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD23	NM_144994.8	c.769A>C	p.Lys257Gln	missense_variant	8/9	ENST00000318357.9	NP_659431.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD23	ENST00000318357.9	c.769A>C	p.Lys257Gln	missense_variant	8/9	1	NM_144994.8	ENSP00000321679.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

Feb 05, 2024

The c.769A>C (p.K257Q) alteration is located in exon 8 (coding exon 8) of the ANKRD23 gene. This alteration results from a A to C substitution at nucleotide position 769, causing the lysine (K) at amino acid position 257 to be replaced by a glutamine (Q). 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	0.21
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.045	T;T;.
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.75	.;T;T
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.31	T;T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.2	L;L;.
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-3.1	D;D;D
REVEL	Benign	0.15
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.015	D;D;D
Polyphen		0.63	P;P;P
Vest4		0.40
MutPred		0.40		Loss of ubiquitination at K257 (P = 0.0412);Loss of ubiquitination at K257 (P = 0.0412);.;
MVP		0.84
MPC		0.56
ClinPred		0.95	D
GERP RS		5.0
Varity_R		0.44
gMVP		0.12

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: chr2-97505517;