6-349386-T-G

Variant names:

• chr6-349386-T-G
• rs7763092
• NM_001286555.3:c.*435T>G

Variant summary

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

The NM_001286555.3(DUSP22):​c.*435T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0162 in 1,019,138 control chromosomes in the GnomAD database, including 7 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 0.029 (2 hom., cov: 59)
  • Exomes 𝑓: 0.014 (5 hom.)
• Consequence: DUSP22 NM_001286555.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0910
• 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=-0.8).
• 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.*435T>G		3_prime_UTR	Exon 7 of 7	NP_001273484.1	Q9NRW4-2
	DUSP22	NM_020185.6		c.508+545T>G		intron	N/A	NP_064570.1	Q9NRW4-1
	DUSP22	NR_104473.3		n.1056T>G		non_coding_transcript_exon	Exon 6 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUSP22	ENST00000419235.7	TSL:2 MANE Select	c.*435T>G		3_prime_UTR	Exon 7 of 7	ENSP00000397459.2	Q9NRW4-2
	DUSP22	ENST00000344450.9	TSL:1	c.508+545T>G		intron	N/A	ENSP00000345281.5	Q9NRW4-1
	DUSP22	ENST00000604971.5	TSL:2	c.*435T>G		3_prime_UTR	Exon 4 of 4	ENSP00000474505.1	S4R3M1

Frequencies

GnomAD3 genomes AF: 0.0284 AC: 4288 AN: 150872 Hom.: 2 Cov.: 59

Gnomad AFR AF: 0.0749

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0200

Gnomad ASJ AF: 0.0208

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00289

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0118

Gnomad OTH AF: 0.0226

GnomAD4 exome AF: 0.0140 AC: 12192 AN: 868148 Hom.: 5 Cov.: 98 AF XY: 0.0139 AC XY: 5605 AN XY: 403488

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

African (AFR) AF: 0.0801 AC: 1322 AN: 16506

American (AMR) AF: 0.0110 AC: 34 AN: 3098

Ashkenazi Jewish (ASJ) AF: 0.0233 AC: 140 AN: 6018

East Asian (EAS) AF: 0.00 AC: 0 AN: 5064

South Asian (SAS) AF: 0.00307 AC: 65 AN: 21140

European-Finnish (FIN) AF: 0.00249 AC: 5 AN: 2012

Middle Eastern (MID) AF: 0.0169 AC: 30 AN: 1776

European-Non Finnish (NFE) AF: 0.0130 AC: 10163 AN: 783230

Other (OTH) AF: 0.0148 AC: 433 AN: 29304

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0286 AC: 4317 AN: 150990 Hom.: 2 Cov.: 59 AF XY: 0.0281 AC XY: 2078 AN XY: 73888

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

African (AFR) AF: 0.0754 AC: 3056 AN: 40532

American (AMR) AF: 0.0199 AC: 303 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.0208 AC: 72 AN: 3462

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5194

South Asian (SAS) AF: 0.00269 AC: 13 AN: 4832

European-Finnish (FIN) AF: 0.00179 AC: 19 AN: 10630

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0118 AC: 801 AN: 67822

Other (OTH) AF: 0.0223 AC: 47 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: 0.0378 Hom.: 8

Asia WGS AF: 0.0110 AC: 38 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.73
DANN	Benign	0.67
PhyloP100		-0.091
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: rs7763092; hg19: chr6-349386;