6-328070-C-T

Variant names:

• chr6-328070-C-T
• rs11757245
• NM_001286555.3:c.139-7044C>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.139-7044C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0162 in 151,386 control chromosomes in the GnomAD database, including 2 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 0.016 (2 hom., cov: 58)
• Consequence: DUSP22 NM_001286555.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29
• Publications: 3 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=-0.86).
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286555.3. 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
	DUSP22	NM_001286555.3	MANE Select	c.139-7044C>T		intron	N/A	NP_001273484.1	Q9NRW4-2
	DUSP22	NM_020185.6		c.139-7044C>T		intron	N/A	NP_064570.1	Q9NRW4-1
	DUSP22	NR_104473.3		n.191+16108C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUSP22	ENST00000419235.7	TSL:2 MANE Select	c.139-7044C>T		intron	N/A	ENSP00000397459.2	Q9NRW4-2
	DUSP22	ENST00000344450.9	TSL:1	c.139-7044C>T		intron	N/A	ENSP00000345281.5	Q9NRW4-1
	DUSP22	ENST00000603453.5	TSL:4	c.-171-7044C>T		intron	N/A	ENSP00000474646.1	S4R3M1

Frequencies

GnomAD3 genomes AF: 0.0162 AC: 2449 AN: 151264 Hom.: 2 Cov.: 58

Gnomad AFR AF: 0.0556

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00551

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00115

Gnomad OTH AF: 0.00864

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

GnomAD4 genome AF: 0.0162 AC: 2456 AN: 151386 Hom.: 2 Cov.: 58 AF XY: 0.0157 AC XY: 1165 AN XY: 74052

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

African (AFR) AF: 0.0556 AC: 2268 AN: 40790

American (AMR) AF: 0.00557 AC: 85 AN: 15260

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00115 AC: 78 AN: 67942

Other (OTH) AF: 0.00855 AC: 18 AN: 2106

⚠️ 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: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.28
DANN	Benign	0.40
PhyloP100		-2.3
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: rs11757245; hg19: chr6-328070;