2-240560901-G-A

Variant names:

• chr2-240560901-G-A
• rs1030136409
• NM_001370465.2:c.217G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001370465.2(DUSP28):​c.217G>A​(p.Asp73Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. D73H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DUSP28 NM_001370465.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.06
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4071548).

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.217G>A	p.Asp73Asn	missense	Exon 1 of 2	NP_001357394.1	Q4G0W2
	ANKMY1	NM_001308375.4		c.50C>T	p.Ser17Leu	missense	Exon 1 of 15	NP_001295304.3	J3KPY5
	DUSP28	NM_001033575.1		c.217G>A	p.Asp73Asn	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.217G>A	p.Asp73Asn	missense	Exon 1 of 2	ENSP00000385885.2	Q4G0W2
	ANKMY1	ENST00000403283.6	TSL:1	c.50C>T	p.Ser17Leu	missense	Exon 1 of 15	ENSP00000383968.1	J3KPY5
	ANKMY1	ENST00000464991.5	TSL:1	n.545C>T		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152010 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1371262 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 680824

African (AFR) AF: 0.00 AC: 0 AN: 28094

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 AF: 0.00000658 AC: 1 AN: 152010 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74276

African (AFR) AF: 0.00 AC: 0 AN: 41414

American (AMR) AF: 0.00 AC: 0 AN: 15276

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10572

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67962

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.22
FATHMM_MKL	Benign	0.62	D
LIST_S2	Uncertain	0.86	D
M_CAP	Pathogenic	0.70	D
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.98	L
PhyloP100		3.1
PrimateAI	Pathogenic	0.95	D
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.094
Sift	Benign	0.56	T
Sift4G	Benign	0.22	T
Polyphen		0.91	P
Vest4		0.43
MutPred		0.40		Loss of disorder (P = 0.1266)
MVP		0.55
MPC		0.63
ClinPred		0.93	D
GERP RS		3.9
PromoterAI		0.029	Neutral
Varity_R		0.29
gMVP		0.47
Mutation Taster		=84/16	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: rs1030136409; hg19: chr2-241500318;