dbSNP rs2278076: MAP2K5:c.*512G>A (chr15-67807262-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_145160.3(MAP2K5):c.*512G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 206,572 control chromosomes in the GnomAD database, including 6,650 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 0.21 ( 4598 hom., cov: 33)

Exomes 𝑓: 0.24 ( 2052 hom. )

Consequence

MAP2K5
NM_145160.3 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0160

Publications

11 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:

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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=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
MAP2K5	NM_145160.3 link	c.*512G>A	downstream_gene_variant	ENST00000178640.10	NP_660143.1	Q13163-1A0A024R5Y2
MAP2K5	NM_002757.4 link	c.*512G>A	downstream_gene_variant		NP_002748.1	Q13163-2A0A024R5X5
MAP2K5	NM_001206804.2 link	c.*512G>A	downstream_gene_variant		NP_001193733.1	Q13163-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP2K5	ENST00000178640.10 link	c.*512G>A		downstream_gene_variant		1	NM_145160.3	ENSP00000178640.5		Q13163-1

Frequencies

GnomAD3 genomes

AF:

0.211

AC:

32137

AN:

152034

Hom.:

4581

Cov.:

show subpopulations

Gnomad AFR

AF:

0.107

Gnomad AMI

AF:

0.122

Gnomad AMR

AF:

0.401

Gnomad ASJ

AF:

0.340

Gnomad EAS

AF:

0.592

Gnomad SAS

AF:

0.341

Gnomad FIN

AF:

0.119

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.202

Gnomad OTH

AF:

0.241

GnomAD4 exome

AF:

0.238

AC:

12940

AN:

54418

Hom.:

2052

AF XY:

0.246

AC XY:

7087

AN XY:

28820

show subpopulations

African (AFR)

AF:

0.100

AC:

170

AN:

1698

American (AMR)

AF:

0.497

AC:

1804

AN:

3630

Ashkenazi Jewish (ASJ)

AF:

0.297

AC:

353

AN:

1190

East Asian (EAS)

AF:

0.578

AC:

1552

AN:

2686

South Asian (SAS)

AF:

0.303

AC:

2464

AN:

8142

European-Finnish (FIN)

AF:

0.115

AC:

270

AN:

2338

Middle Eastern (MID)

AF:

0.239

AC:

AN:

176

European-Non Finnish (NFE)

AF:

0.180

AC:

5749

AN:

32008

Other (OTH)

AF:

0.210

AC:

536

AN:

2550

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

448

897

1345

1794

2242

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

276

414

552

690

<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:

0.211

AC:

32167

AN:

152154

Hom.:

4598

Cov.:

AF XY:

0.216

AC XY:

16038

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.107

AC:

4445

AN:

41532

American (AMR)

AF:

0.402

AC:

6148

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.340

AC:

1180

AN:

3466

East Asian (EAS)

AF:

0.593

AC:

3056

AN:

5150

South Asian (SAS)

AF:

0.342

AC:

1646

AN:

4808

European-Finnish (FIN)

AF:

0.119

AC:

1262

AN:

10624

Middle Eastern (MID)

AF:

0.276

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.202

AC:

13723

AN:

67970

Other (OTH)

AF:

0.244

AC:

515

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1219

2438

3658

4877

6096

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

340

680

1020

1360

1700

<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:

0.218

Hom.:

1773

Bravo

AF:

0.232

Asia WGS

AF:

0.468

AC:

1627

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.6

(source)

DANN

Benign

0.72

PhyloP100

0.016

Splicing

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