2-96840251-C-A

Variant names:

• chr2-96840251-C-A
• rs570484917
• NM_144994.8:c.605G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144994.8(ANKRD23):​c.605G>T​(p.Arg202Leu) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R202Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ANKRD23 NM_144994.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.868
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2003695).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144994.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD23	NM_144994.8	MANE Select	c.605G>T	p.Arg202Leu	missense	Exon 6 of 9	NP_659431.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD23	ENST00000318357.9	TSL:1 MANE Select	c.605G>T	p.Arg202Leu	missense	Exon 6 of 9	ENSP00000321679.4	Q86SG2-1
	ANKRD23	ENST00000962363.1		c.614G>T	p.Arg205Leu	missense	Exon 6 of 9	ENSP00000632422.1
	ANKRD23	ENST00000870651.1		c.605G>T	p.Arg202Leu	missense	Exon 6 of 9	ENSP00000540710.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.074	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.81	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.91	L
PhyloP100		0.87
PrimateAI	Benign	0.20	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.11
Sift	Benign	0.031	D
Sift4G	Benign	0.14	T
Polyphen		0.12	B
Vest4		0.37
MutPred		0.53		Loss of MoRF binding (P = 0.0059)
MVP		0.27
MPC		0.24
ClinPred		0.18	T
GERP RS		-3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.35
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs570484917; hg19: chr2-97505988;