2-240560806-C-T

Variant names:

• chr2-240560806-C-T
• rs1189324201
• NM_001370465.2:c.122C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001370465.2(DUSP28):​c.122C>T​(p.Ala41Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000775 in 1,289,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 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. A41G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.8e-7 (0 hom.)
• Consequence: DUSP28 NM_001370465.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.572
• Publications: 0 publications found

Genes affected

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

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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.032311946).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370465.2. 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.122C>T	p.Ala41Val	missense	Exon 1 of 2	NP_001357394.1	Q4G0W2
	ANKMY1	NM_001308375.4		c.145G>A	p.Ala49Thr	missense	Exon 1 of 15	NP_001295304.3	J3KPY5
	DUSP28	NM_001033575.1		c.122C>T	p.Ala41Val	missense	Exon 1 of 3	NP_001028747.1	Q4G0W2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUSP28	ENST00000405954.2	TSL:1 MANE Select	c.122C>T	p.Ala41Val	missense	Exon 1 of 2	ENSP00000385885.2	Q4G0W2
	ANKMY1	ENST00000403283.6	TSL:1	c.145G>A	p.Ala49Thr	missense	Exon 1 of 15	ENSP00000383968.1	J3KPY5
	ANKMY1	ENST00000464991.5	TSL:1	n.640G>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.75e-7 AC: 1 AN: 1289890 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 634964

African (AFR) AF: 0.00 AC: 0 AN: 26130

American (AMR) AF: 0.00 AC: 0 AN: 19710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21422

East Asian (EAS) AF: 0.00 AC: 0 AN: 28394

South Asian (SAS) AF: 0.00 AC: 0 AN: 67238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32256

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3930

European-Non Finnish (NFE) AF: 9.64e-7 AC: 1 AN: 1037568

Other (OTH) AF: 0.00 AC: 0 AN: 53242

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	4.6
DANN	Benign	0.95
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.57
PROVEAN	Benign	0.12	N
REVEL	Benign	0.019
Sift	Pathogenic	0.0	D
Vest4		0.076
MutPred		0.20		Gain of phosphorylation at A49 (P = 0.0163)
MVP		0.040
ClinPred		0.074	T
GERP RS		-0.70
PromoterAI		-0.093	Neutral
Varity_R		0.064
Mutation Taster		=89/11	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: rs1189324201; hg19: chr2-241500223; COSMIC: COSV108017820; COSMIC: COSV108017820;