rs3800250

Variant names:

• chr6-334825-C-T
• rs3800250
• NM_001286555.3:c.139-289C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001286555.3(DUSP22):​c.139-289C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0789 in 148,786 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.079 (26 hom., cov: 61)
• Consequence: DUSP22 NM_001286555.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18
• Publications: 4 publications found

Genes affected

DUSP22 (HGNC:16077): (dual specificity phosphatase 22) Enables non-membrane spanning protein tyrosine phosphatase activity and protein tyrosine kinase binding activity. Involved in several processes, including cellular response to epidermal growth factor stimulus; negative regulation of focal adhesion assembly; and negative regulation of non-membrane spanning protein tyrosine kinase activity. Acts upstream of or within negative regulation of transcription by RNA polymerase II. Located in plasma membrane. Part of cytoplasm; filamentous actin; and leading edge of lamellipodium. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BS2: High Homozygotes in GnomAd4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DUSP22	NM_001286555.3	c.139-289C>T		intron_variant	Intron 3 of 6	ENST00000419235.7	NP_001273484.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DUSP22	ENST00000419235.7	c.139-289C>T		intron_variant	Intron 3 of 6	2	NM_001286555.3	ENSP00000397459.2

Frequencies

GnomAD3 genomes AF: 0.0789 AC: 11729 AN: 148668 Hom.: 26 Cov.: 61

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0982

Gnomad ASJ AF: 0.0199

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0349

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.0292

Gnomad OTH AF: 0.0701

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0789 AC: 11744 AN: 148786 Hom.: 26 Cov.: 61 AF XY: 0.0814 AC XY: 5917 AN XY: 72676

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.154 AC: 6104 AN: 39608

American (AMR) AF: 0.0983 AC: 1462 AN: 14870

Ashkenazi Jewish (ASJ) AF: 0.0199 AC: 69 AN: 3462

East Asian (EAS) AF: 0.220 AC: 1091 AN: 4962

South Asian (SAS) AF: 0.113 AC: 526 AN: 4654

European-Finnish (FIN) AF: 0.0349 AC: 365 AN: 10466

Middle Eastern (MID) AF: 0.0274 AC: 8 AN: 292

European-Non Finnish (NFE) AF: 0.0293 AC: 1974 AN: 67484

Other (OTH) AF: 0.0694 AC: 144 AN: 2076

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0677 Hom.: 36

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	9.5
DANN	Benign	0.67
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs3800250; hg19: chr6-334825; COSMIC: COSV60529515; COSMIC: COSV60529515;