chr2-96143592-T-A

Variant names:

• chr2-96143592-T-A
• rs1724120
• NM_004418.4:c.*231A>T

Variant summary

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

The NM_004418.4(DUSP2):​c.*231A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000023 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DUSP2 NM_004418.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.338
• Publications: 27 publications found

Genes affected

DUSP2 (HGNC:3068): (dual specificity phosphatase 2) The protein encoded by this gene is a member of the dual specificity protein phosphatase subfamily. These phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine/threonine and phosphotyrosine residues. They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which are associated with cellular proliferation and differentiation. Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases, different tissue distribution and subcellular localization, and different modes of inducibility of their expression by extracellular stimuli. This gene product inactivates ERK1 and ERK2, is predominantly expressed in hematopoietic tissues, and is localized in the nucleus. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004418.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUSP2	NM_004418.4	MANE Select	c.*231A>T		3_prime_UTR	Exon 4 of 4	NP_004409.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUSP2	ENST00000288943.5	TSL:1 MANE Select	c.*231A>T		3_prime_UTR	Exon 4 of 4	ENSP00000288943.4
	DUSP2	ENST00000718436.1		c.*231A>T		3_prime_UTR	Exon 4 of 4	ENSP00000520821.1
	DUSP2	ENST00000488952.1	TSL:2	n.*137A>T		downstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000235 AC: 1 AN: 426224 Hom.: 0 Cov.: 4 AF XY: 0.00000448 AC XY: 1 AN XY: 223114

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

African (AFR) AF: 0.00 AC: 0 AN: 11988

American (AMR) AF: 0.00 AC: 0 AN: 17096

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13010

East Asian (EAS) AF: 0.00 AC: 0 AN: 28842

South Asian (SAS) AF: 0.0000230 AC: 1 AN: 43424

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27704

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1840

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 257864

Other (OTH) AF: 0.00 AC: 0 AN: 24456

⚠️ 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 Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.4
DANN	Benign	0.58
PhyloP100		-0.34

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: rs1724120; hg19: chr2-96809331;