Variant chr12-89350469-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001946.4(DUSP6):c.838+119A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,029,348 control chromosomes in the GnomAD database, including 7,218 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1246 hom., cov: 32)

Exomes 𝑓: 0.11 ( 5972 hom. )

Consequence

DUSP6
NM_001946.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.00400

Variant links:

Genes affected

DUSP6 (HGNC:3072): (dual specificity phosphatase 6) 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 ERK2, is expressed in a variety of tissues with the highest levels in heart and pancreas, and unlike most other members of this family, is localized in the cytoplasm. Mutations in this gene have been associated with congenital hypogonadotropic hypogonadism. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2014]

DUSP6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 12-89350469-T-G is Benign according to our data. Variant chr12-89350469-T-G is described in ClinVar as [Benign]. Clinvar id is 1225295.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUSP6	NM_001946.4 linkuse as main transcript	c.838+119A>C		intron_variant		ENST00000279488.8	NP_001937.2
DUSP6	NM_022652.4 linkuse as main transcript	c.401-908A>C		intron_variant			NP_073143.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
DUSP6	ENST00000279488.8 linkuse as main transcript	c.838+119A>C	intron_variant	1	NM_001946.4	ENSP00000279488	P1	Q16828-1
DUSP6	ENST00000308385.6 linkuse as main transcript	c.401-908A>C	intron_variant	1		ENSP00000307835		Q16828-2
DUSP6	ENST00000547291.1 linkuse as main transcript	c.463+119A>C	intron_variant	2		ENSP00000449838
DUSP6	ENST00000547140.1 linkuse as main transcript	n.524+119A>C	intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.125

AC:

19004

AN:

152016

Hom.:

1244

Cov.:

show subpopulations

Gnomad AFR

AF:

0.141

Gnomad AMI

AF:

0.250

Gnomad AMR

AF:

0.173

Gnomad ASJ

AF:

0.103

Gnomad EAS

AF:

0.0231

Gnomad SAS

AF:

0.0912

Gnomad FIN

AF:

0.120

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.115

Gnomad OTH

AF:

0.124

GnomAD4 exome

AF:

0.113

AC:

99136

AN:

877214

Hom.:

5972

AF XY:

0.112

AC XY:

49789

AN XY:

446132

show subpopulations

Gnomad4 AFR exome

AF:

0.136

Gnomad4 AMR exome

AF:

0.191

Gnomad4 ASJ exome

AF:

0.109

Gnomad4 EAS exome

AF:

0.0237

Gnomad4 SAS exome

AF:

0.0975

Gnomad4 FIN exome

AF:

0.108

Gnomad4 NFE exome

AF:

0.116

Gnomad4 OTH exome

AF:

0.115

GnomAD4 genome

AF:

0.125

AC:

19024

AN:

152134

Hom.:

1246

Cov.:

AF XY:

0.125

AC XY:

9287

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.140

Gnomad4 AMR

AF:

0.173

Gnomad4 ASJ

AF:

0.103

Gnomad4 EAS

AF:

0.0232

Gnomad4 SAS

AF:

0.0917

Gnomad4 FIN

AF:

0.120

Gnomad4 NFE

AF:

0.115

Gnomad4 OTH

AF:

0.124

Alfa

AF:

0.122

Hom.:

125

Bravo

AF:

0.132

Asia WGS

AF:

0.0690

AC:

239

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.6

DANN

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over