12-89350325-C-T

Position:

• chr12-89350325-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001946.4(DUSP6):​c.838+263G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.007 in 152,266 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0070 (4 hom., cov: 32)
• Consequence: DUSP6 NM_001946.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.137

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 12-89350325-C-T is Benign according to our data. Variant chr12-89350325-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1218279.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 1066 AD,Digenic gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUSP6	NM_001946.4	c.838+263G>A		intron_variant		ENST00000279488.8	NP_001937.2
DUSP6	NM_022652.4	c.401-764G>A		intron_variant			NP_073143.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUSP6	ENST00000279488.8	c.838+263G>A		intron_variant		1	NM_001946.4	ENSP00000279488.6
DUSP6	ENST00000308385.6	c.401-764G>A		intron_variant		1		ENSP00000307835.6
DUSP6	ENST00000547291.1	c.463+263G>A		intron_variant		2		ENSP00000449838.1
DUSP6	ENST00000547140.1	n.524+263G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.00701 AC: 1066 AN: 152148 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00225

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00465

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00321

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0123

Gnomad OTH AF: 0.00525

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

GnomAD4 genome AF: 0.00700 AC: 1066 AN: 152266 Hom.: 4 Cov.: 32 AF XY: 0.00666 AC XY: 496 AN XY: 74456

Gnomad4 AFR AF: 0.00224

Gnomad4 AMR AF: 0.00464

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00270

Gnomad4 FIN AF: 0.00321

Gnomad4 NFE AF: 0.0123

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.0118 Hom.: 2

Bravo AF: 0.00695

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.7
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs111837731; hg19: chr12-89744102;