chr6-348096-C-T

Variant names:

• chr6-348096-C-T
• rs200952897
• NM_001286555.3:c.264-7C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001286555.3(DUSP22):​c.264-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00312 in 1,611,350 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0029 (0 hom., cov: 61)
  • Exomes 𝑓: 0.0032 (0 hom.)
• Consequence: DUSP22 NM_001286555.3 splice_region, intron
• Scores: Splicing: ADA: 0.0004093
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.225
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Variant has high frequency in the MID (0.00849) population. However there is too low homozygotes in high coverage region: (expected more than 3, got 0).
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 6-348096-C-T is Benign according to our data. Variant chr6-348096-C-T is described in ClinVar as Benign. ClinVar VariationId is 780116.Status of the report is criteria_provided_single_submitter, 1 stars.

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.264-7C>T		splice_region intron	N/A	NP_001273484.1	Q9NRW4-2
	DUSP22	NM_020185.6		c.264-7C>T		splice_region intron	N/A	NP_064570.1	Q9NRW4-1
	DUSP22	NR_104473.3		n.267-7C>T		splice_region intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUSP22	ENST00000419235.7	TSL:2 MANE Select	c.264-7C>T		splice_region intron	N/A	ENSP00000397459.2	Q9NRW4-2
	DUSP22	ENST00000344450.9	TSL:1	c.264-7C>T		splice_region intron	N/A	ENSP00000345281.5	Q9NRW4-1
	DUSP22	ENST00000603453.5	TSL:4	c.-46-7C>T		splice_region intron	N/A	ENSP00000474646.1	S4R3M1

Frequencies

GnomAD3 genomes AF: 0.00285 AC: 434 AN: 152150 Hom.: 0 Cov.: 61

Gnomad AFR AF: 0.00147

Gnomad AMI AF: 0.0365

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.00412

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00285 AC: 714 AN: 250610 AF XY: 0.00303

Gnomad AFR exome AF: 0.00166

Gnomad AMR exome AF: 0.00278

Gnomad ASJ exome AF: 0.00139

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000788

Gnomad NFE exome AF: 0.00430

Gnomad OTH exome AF: 0.00311

GnomAD4 exome AF: 0.00315 AC: 4599 AN: 1459084 Hom.: 0 Cov.: 35 AF XY: 0.00320 AC XY: 2324 AN XY: 725776

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

African (AFR) AF: 0.000777 AC: 26 AN: 33468

American (AMR) AF: 0.00271 AC: 121 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.00226 AC: 59 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00173 AC: 149 AN: 86192

European-Finnish (FIN) AF: 0.000919 AC: 49 AN: 53332

Middle Eastern (MID) AF: 0.0106 AC: 61 AN: 5740

European-Non Finnish (NFE) AF: 0.00357 AC: 3966 AN: 1109580

Other (OTH) AF: 0.00279 AC: 168 AN: 60310

⚠️ 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: 0.00286 AC: 435 AN: 152266 Hom.: 0 Cov.: 61 AF XY: 0.00282 AC XY: 210 AN XY: 74472

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

African (AFR) AF: 0.00149 AC: 62 AN: 41574

American (AMR) AF: 0.00157 AC: 24 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4830

European-Finnish (FIN) AF: 0.000659 AC: 7 AN: 10628

Middle Eastern (MID) AF: 0.0171 AC: 5 AN: 292

European-Non Finnish (NFE) AF: 0.00412 AC: 280 AN: 67958

Other (OTH) AF: 0.00473 AC: 10 AN: 2116

⚠️ 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: 0.00334 Hom.: 0

EpiCase AF: 0.00492

EpiControl AF: 0.00499

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	7.7
DANN	Benign	0.70
PhyloP100		0.23
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00041
dbscSNV1_RF	Benign	0.028
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: rs200952897; hg19: chr6-348096;