chr2-240560701-C-T

Variant names:

• chr2-240560701-C-T
• rs774218472
• NM_001370465.2:c.17C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001370465.2(DUSP28):​c.17C>T​(p.Ala6Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,528,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000058 (0 hom.)
• Consequence: DUSP28 NM_001370465.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.193
• 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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0846957).

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.17C>T	p.Ala6Val	missense	Exon 1 of 2	NP_001357394.1	Q4G0W2
	DUSP28	NM_001033575.1		c.17C>T	p.Ala6Val	missense	Exon 1 of 3	NP_001028747.1	Q4G0W2
	ANKMY1	NM_001354023.3		c.-334+30G>A		intron	N/A	NP_001340952.1	J3KQ21

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUSP28	ENST00000405954.2	TSL:1 MANE Select	c.17C>T	p.Ala6Val	missense	Exon 1 of 2	ENSP00000385885.2	Q4G0W2
	ANKMY1	ENST00000403283.6	TSL:1	c.220+30G>A		intron	N/A	ENSP00000383968.1	J3KPY5
	ANKMY1	ENST00000405002.6	TSL:1	c.-122+30G>A		intron	N/A	ENSP00000385145.1	J3KQ07

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152138 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 156604 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000581 AC: 8 AN: 1376724 Hom.: 0 Cov.: 31 AF XY: 0.00000438 AC XY: 3 AN XY: 684792

African (AFR) AF: 0.000212 AC: 6 AN: 28316

American (AMR) AF: 0.00 AC: 0 AN: 33318

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24204

East Asian (EAS) AF: 0.00 AC: 0 AN: 31888

South Asian (SAS) AF: 0.00 AC: 0 AN: 78962

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35892

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5312

European-Non Finnish (NFE) AF: 9.24e-7 AC: 1 AN: 1081944

Other (OTH) AF: 0.0000176 AC: 1 AN: 56888

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152138 Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6 AN XY: 74336

African (AFR) AF: 0.000265 AC: 11 AN: 41444

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000642

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	Benign	0.14
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.0097	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.5	L
PhyloP100		-0.19
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-0.27	N
REVEL	Benign	0.074
Sift	Uncertain	0.020	D
Sift4G	Benign	0.071	T
Polyphen		0.11	B
Vest4		0.32
MutPred		0.30		Gain of helix (P = 0.0854)
MVP		0.085
MPC		0.33
ClinPred		0.31	T
GERP RS		2.4
PromoterAI		-0.11	Neutral
Varity_R		0.093
gMVP		0.40
Mutation Taster		=99/1	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: rs774218472; hg19: chr2-241500118;