rs41305272

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The ENST00000178640.10(MAP2K5):​c.*355C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0319 in 572,126 control chromosomes in the GnomAD database, including 372 homozygotes. 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: 𝑓 0.024 ( 58 hom., cov: 33)
Exomes 𝑓: 0.035 ( 314 hom. )

Consequence

MAP2K5
ENST00000178640.10 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.42
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0238 (3625/152330) while in subpopulation NFE AF= 0.0401 (2725/68022). AF 95% confidence interval is 0.0388. There are 58 homozygotes in gnomad4. There are 1651 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 3625 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MAP2K5NM_145160.3 linkuse as main transcriptc.*355C>T 3_prime_UTR_variant 22/22 ENST00000178640.10 NP_660143.1
MAP2K5NM_001206804.2 linkuse as main transcriptc.*355C>T 3_prime_UTR_variant 22/22 NP_001193733.1
MAP2K5NM_002757.4 linkuse as main transcriptc.*355C>T 3_prime_UTR_variant 21/21 NP_002748.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MAP2K5ENST00000178640.10 linkuse as main transcriptc.*355C>T 3_prime_UTR_variant 22/221 NM_145160.3 ENSP00000178640 P1Q13163-1

Frequencies

GnomAD3 genomes
AF:
0.0238
AC:
3627
AN:
152212
Hom.:
59
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00736
Gnomad AMI
AF:
0.0888
Gnomad AMR
AF:
0.0165
Gnomad ASJ
AF:
0.0205
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00559
Gnomad FIN
AF:
0.0108
Gnomad MID
AF:
0.0411
Gnomad NFE
AF:
0.0401
Gnomad OTH
AF:
0.0177
GnomAD4 exome
AF:
0.0348
AC:
14610
AN:
419796
Hom.:
314
Cov.:
7
AF XY:
0.0333
AC XY:
7119
AN XY:
213960
show subpopulations
Gnomad4 AFR exome
AF:
0.00507
Gnomad4 AMR exome
AF:
0.0168
Gnomad4 ASJ exome
AF:
0.0179
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00822
Gnomad4 FIN exome
AF:
0.0169
Gnomad4 NFE exome
AF:
0.0429
Gnomad4 OTH exome
AF:
0.0327
GnomAD4 genome
AF:
0.0238
AC:
3625
AN:
152330
Hom.:
58
Cov.:
33
AF XY:
0.0222
AC XY:
1651
AN XY:
74490
show subpopulations
Gnomad4 AFR
AF:
0.00734
Gnomad4 AMR
AF:
0.0165
Gnomad4 ASJ
AF:
0.0205
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00580
Gnomad4 FIN
AF:
0.0108
Gnomad4 NFE
AF:
0.0401
Gnomad4 OTH
AF:
0.0175
Alfa
AF:
0.0328
Hom.:
37
Bravo
AF:
0.0236
Asia WGS
AF:
0.00577
AC:
20
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.51
CADD
Benign
8.5
DANN
Benign
0.78

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

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

Other links and lift over

dbSNP: rs41305272; hg19: chr15-68099443; API