dbSNP rs41305272: MAP2K5:c.*355C>T (chr15-67807105-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_145160.3(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
NM_145160.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.42

Publications

12 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 3625 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MAP2K5	NM_145160.3 link	c.*355C>T	3_prime_UTR_variant	Exon 22 of 22	ENST00000178640.10	NP_660143.1	Q13163-1A0A024R5Y2
MAP2K5	NM_002757.4 link	c.*355C>T	3_prime_UTR_variant	Exon 21 of 21		NP_002748.1	Q13163-2A0A024R5X5
MAP2K5	NM_001206804.2 link	c.*355C>T	3_prime_UTR_variant	Exon 22 of 22		NP_001193733.1	Q13163-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP2K5	ENST00000178640.10 link	c.*355C>T		3_prime_UTR_variant	Exon 22 of 22	1	NM_145160.3	ENSP00000178640.5		Q13163-1

Frequencies

GnomAD3 genomes

AF:

0.0238

AC:

3627

AN:

152212

Hom.:

Cov.:

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.:

AF XY:

0.0333

AC XY:

7119

AN XY:

213960

show subpopulations

African (AFR)

AF:

0.00507

AC:

AN:

10060

American (AMR)

AF:

0.0168

AC:

196

AN:

11654

Ashkenazi Jewish (ASJ)

AF:

0.0179

AC:

129

AN:

7196

East Asian (EAS)

AF:

0.00

AC:

AN:

11514

South Asian (SAS)

AF:

0.00822

AC:

369

AN:

44896

European-Finnish (FIN)

AF:

0.0169

AC:

181

AN:

10720

Middle Eastern (MID)

AF:

0.0407

AC:

AN:

1228

European-Non Finnish (NFE)

AF:

0.0429

AC:

13034

AN:

304170

Other (OTH)

AF:

0.0327

AC:

600

AN:

18358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

655

1310

1966

2621

3276

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

430

860

1290

1720

2150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0238

AC:

3625

AN:

152330

Hom.:

Cov.:

AF XY:

0.0222

AC XY:

1651

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.00734

AC:

305

AN:

41568

American (AMR)

AF:

0.0165

AC:

252

AN:

15314

Ashkenazi Jewish (ASJ)

AF:

0.0205

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.00580

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0108

AC:

115

AN:

10622

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0401

AC:

2725

AN:

68022

Other (OTH)

AF:

0.0175

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

172

345

517

690

862

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0320

Hom.:

Bravo

AF:

0.0236

Asia WGS

AF:

0.00577

AC:

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

(source)

DANN

Benign

0.78

PhyloP100

1.4

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over