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15-67692480-C-T

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

2
Splicing: ADA: 0.000004392
2

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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.62).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.237 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1096 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MAP2K5NM_145160.3 linkuse as main transcriptc.849C>T p.Asp283= splice_region_variant, synonymous_variant 14/22 ENST00000178640.10
MAP2K5NM_002757.4 linkuse as main transcriptc.849C>T p.Asp283= splice_region_variant, synonymous_variant 14/21
MAP2K5NM_001206804.2 linkuse as main transcriptc.741C>T p.Asp247= splice_region_variant, synonymous_variant 14/22
MAP2K5XR_007064474.1 linkuse as main transcriptn.1433C>T splice_region_variant, non_coding_transcript_exon_variant 13/14

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MAP2K5ENST00000178640.10 linkuse as main transcriptc.849C>T p.Asp283= splice_region_variant, synonymous_variant 14/221 NM_145160.3 P1Q13163-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00720
AC:
1096
AN:
152154
Hom.:
10
Cov.:
32
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.:
3
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.:
29
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00720
AC:
1096
AN:
152272
Hom.:
10
Cov.:
32
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.:
18
Bravo
AF:
0.00680
Asia WGS
AF:
0.00144
AC:
5
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 submitterclinical testingInvitaeJul 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.

Other links and lift over

dbSNP: rs55966838; hg19: chr15-67984818; COSMIC: COSV51613937; API