2-240507618-C-T

Variant names:

• chr2-240507618-C-T
• NM_001282771.3:c.2468G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001282771.3(ANKMY1):​c.2468G>A​(p.Cys823Tyr) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ANKMY1 NM_001282771.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.03
• Publications: 0 publications found

Genes affected

ANKMY1 (HGNC:20987): (ankyrin repeat and MYND domain containing 1) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.839

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282771.3. 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
	ANKMY1	NM_001282771.3	MANE Select	c.2468G>A	p.Cys823Tyr	missense	Exon 13 of 18	NP_001269700.1	J3KQ21
	ANKMY1	NM_001354023.3		c.2468G>A	p.Cys823Tyr	missense	Exon 14 of 19	NP_001340952.1	J3KQ21
	ANKMY1	NM_001393462.1		c.2384G>A	p.Cys795Tyr	missense	Exon 13 of 18	NP_001380391.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKMY1	ENST00000401804.6	TSL:1 MANE Select	c.2468G>A	p.Cys823Tyr	missense	Exon 13 of 18	ENSP00000385887.1	J3KQ21
	ANKMY1	ENST00000272972.7	TSL:1	c.2201G>A	p.Cys734Tyr	missense	Exon 12 of 17	ENSP00000272972.3	Q9P2S6-1
	ANKMY1	ENST00000403283.6	TSL:1	c.1907G>A	p.Cys636Tyr	missense	Exon 10 of 15	ENSP00000383968.1	J3KPY5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Uncertain	0.048	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Benign	0.94
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.035
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.84	T
M_CAP	Uncertain	0.19	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	-0.66	N
PhyloP100		3.0
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-9.5	D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.056	T
Polyphen		1.0	D
Vest4		0.85
MutPred		0.60		Gain of helix (P = 0.0128)
MVP		0.77
ClinPred		1.0	D
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.80
gMVP		0.73
Mutation Taster		=81/19	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

hg19: chr2-241447035;