2-240560901-G-T

Variant names:

• chr2-240560901-G-T
• rs1030136409
• ENST00000403283.6:c.50C>A

Variant summary

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

The NM_001308375.4(ANKMY1):​c.50C>A​(p.Ser17*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANKMY1 NM_001308375.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.06
• 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]

DUSP28 (HGNC:33237): (dual specificity phosphatase 28) Enables phosphatase activity. Involved in dephosphorylation. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001308375.4. 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
	DUSP28	NM_001370465.2	MANE Select	c.217G>T	p.Asp73Tyr	missense	Exon 1 of 2	NP_001357394.1	Q4G0W2
	ANKMY1	NM_001308375.4		c.50C>A	p.Ser17*	stop_gained	Exon 1 of 15	NP_001295304.3	J3KPY5
	DUSP28	NM_001033575.1		c.217G>T	p.Asp73Tyr	missense	Exon 1 of 3	NP_001028747.1	Q4G0W2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKMY1	ENST00000403283.6	TSL:1	c.50C>A	p.Ser17*	stop_gained	Exon 1 of 15	ENSP00000383968.1	J3KPY5
	DUSP28	ENST00000405954.2	TSL:1 MANE Select	c.217G>T	p.Asp73Tyr	missense	Exon 1 of 2	ENSP00000385885.2	Q4G0W2
	ANKMY1	ENST00000464991.5	TSL:1	n.545C>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1371264 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 680824

African (AFR) AF: 0.00 AC: 0 AN: 28096

American (AMR) AF: 0.00 AC: 0 AN: 32326

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24062

East Asian (EAS) AF: 0.00 AC: 0 AN: 31782

South Asian (SAS) AF: 0.00 AC: 0 AN: 78070

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35018

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4010

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1081162

Other (OTH) AF: 0.00 AC: 0 AN: 56738

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	30
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.51	D
Eigen	Benign	0.12
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.62	D
LIST_S2	Uncertain	0.89	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		3.1
PrimateAI	Pathogenic	0.95	D
PROVEAN	Uncertain	-4.1	D
REVEL	Uncertain	0.36
Sift	Benign	0.32	T
Sift4G	Uncertain	0.017	D
Polyphen		1.0	D
Vest4		0.64
MutPred		0.44		Loss of disorder (P = 0.0186)
MVP		0.58
MPC		1.2
ClinPred		1.0	D
GERP RS		3.9
PromoterAI		0.030	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.52
gMVP		0.71
Mutation Taster		=50/150	disease causing (fs/PTC)

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: rs1030136409; hg19: chr2-241500318;