Variant 15-67692480-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_145160.3(MAP2K5):c.849C>T(p.Asp283=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 1,612,470 control chromosomes in the GnomAD database, including 122 homozygotes. 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 0.0072 ( 10 hom., cov: 32)

Exomes 𝑓: 0.011 ( 112 hom. )

Consequence

MAP2K5
NM_145160.3 splice_region, synonymous

Scores

Splicing: ADA: 0.000004392

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.237

Variant links:

Genes affected

MAP2K5 (HGNC:6845): (mitogen-activated protein kinase kinase 5) The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase specifically interacts with and activates MAPK7/ERK5. This kinase itself can be phosphorylated and activated by MAP3K3/MEKK3, as well as by atypical protein kinase C isoforms (aPKCs). The signal cascade mediated by this kinase is involved in growth factor stimulated cell proliferation and muscle cell differentiation. Three alternatively spliced transcript variants of this gene encoding distinct isoforms have been described. [provided by RefSeq, May 2011]

MAP2K5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 15-67692480-C-T is Benign according to our data. Variant chr15-67692480-C-T is described in ClinVar as [Benign]. Clinvar id is 708695.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.237 with no splicing effect.

BS2

High AC in GnomAd4 at 1096 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MAP2K5	NM_145160.3 linkuse as main transcript	c.849C>T	p.Asp283=	splice_region_variant, synonymous_variant	14/22	ENST00000178640.10
MAP2K5	NM_002757.4 linkuse as main transcript	c.849C>T	p.Asp283=	splice_region_variant, synonymous_variant	14/21
MAP2K5	NM_001206804.2 linkuse as main transcript	c.741C>T	p.Asp247=	splice_region_variant, synonymous_variant	14/22
MAP2K5	XR_007064474.1 linkuse as main transcript	n.1433C>T		splice_region_variant, non_coding_transcript_exon_variant	13/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP2K5	ENST00000178640.10 linkuse as main transcript	c.849C>T	p.Asp283=	splice_region_variant, synonymous_variant	14/22	1	NM_145160.3	P1	Q13163-1

Frequencies

GnomAD3 genomes

AF:

0.00720

AC:

1096

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00186

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.00785

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.00632

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0116

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00718

AC:

1802

AN:

251098

Hom.:

AF XY:

0.00715

AC XY:

970

AN XY:

135704

show subpopulations

Gnomad AFR exome

AF:

0.00185

Gnomad AMR exome

AF:

0.00426

Gnomad ASJ exome

AF:

0.000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00311

Gnomad FIN exome

AF:

0.00730

Gnomad NFE exome

AF:

0.0116

Gnomad OTH exome

AF:

0.00685

GnomAD4 exome

AF:

0.0109

AC:

15987

AN:

1460198

Hom.:

112

Cov.:

AF XY:

0.0106

AC XY:

7698

AN XY:

726516

show subpopulations

Gnomad4 AFR exome

AF:

0.00162

Gnomad4 AMR exome

AF:

0.00412

Gnomad4 ASJ exome

AF:

0.00130

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.00386

Gnomad4 FIN exome

AF:

0.00736

Gnomad4 NFE exome

AF:

0.0131

Gnomad4 OTH exome

AF:

0.00733

GnomAD4 genome

AF:

0.00720

AC:

1096

AN:

152272

Hom.:

Cov.:

AF XY:

0.00747

AC XY:

556

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00185

Gnomad4 AMR

AF:

0.00784

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.00632

Gnomad4 NFE

AF:

0.0116

Gnomad4 OTH

AF:

0.00804

Alfa

AF:

0.0103

Hom.:

Bravo

AF:

0.00680

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0114

EpiControl

AF:

0.0105

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

5.9

DANN

Benign

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0000044

dbscSNV1_RF

Benign

0.0

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

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