chr2-240560701-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001370465.2(DUSP28):​c.17C>A​(p.Ala6Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000654 in 1,528,972 control chromosomes in the GnomAD database, including 1 homozygotes. 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. A6V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000058 (1 hom.)
• Consequence: DUSP28 NM_001370465.2 missense
• Clinical Significance: Not reported in ClinVar
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05817187).

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>A	p.Ala6Asp	missense	Exon 1 of 2	NP_001357394.1	Q4G0W2
	DUSP28	NM_001033575.1		c.17C>A	p.Ala6Asp	missense	Exon 1 of 3	NP_001028747.1	Q4G0W2
	ANKMY1	NM_001354023.3		c.-334+30G>T		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>A	p.Ala6Asp	missense	Exon 1 of 2	ENSP00000385885.2	Q4G0W2
	ANKMY1	ENST00000403283.6	TSL:1	c.220+30G>T		intron	N/A	ENSP00000383968.1	J3KPY5
	ANKMY1	ENST00000405002.6	TSL:1	c.-122+30G>T		intron	N/A	ENSP00000385145.1	J3KQ07

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152138 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.0000511 AC: 8 AN: 156604 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000349

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.: 1 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 684792

African (AFR) AF: 0.00 AC: 0 AN: 28316

American (AMR) AF: 0.000240 AC: 8 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: 0.00 AC: 0 AN: 1081944

Other (OTH) AF: 0.00 AC: 0 AN: 56888

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152248 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74456

African (AFR) AF: 0.00 AC: 0 AN: 41564

American (AMR) AF: 0.000131 AC: 2 AN: 15310

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67984

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.0000633 AC: 7

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	8.5
DANN	Benign	0.95
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.2	L
PhyloP100		-0.19
PrimateAI	Pathogenic	0.80	D
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.14
Sift	Benign	0.030	D
Sift4G	Benign	0.21	T
Polyphen		0.64	P
Vest4		0.27
MutPred		0.29		Gain of relative solvent accessibility (P = 0.0479)
MVP		0.17
MPC		0.50
ClinPred		0.11	T
GERP RS		2.4
PromoterAI		0.13	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.25
gMVP		0.47
Mutation Taster		=100/0	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;