dbSNP rs7172298: MAP2K5:c.253-109T>C (chr15-67580645-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_145160.3(MAP2K5):c.253-109T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 727,766 control chromosomes in the GnomAD database, including 74,477 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 0.41 ( 14071 hom., cov: 32)

Exomes 𝑓: 0.44 ( 60406 hom. )

Consequence

MAP2K5
NM_145160.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.10

Publications

4 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP2K5	NM_145160.3 link	c.253-109T>C		intron_variant	Intron 3 of 21	ENST00000178640.10	NP_660143.1	Q13163-1A0A024R5Y2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP2K5	ENST00000178640.10 link	c.253-109T>C		intron_variant	Intron 3 of 21	1	NM_145160.3	ENSP00000178640.5		Q13163-1

Frequencies

GnomAD3 genomes

AF:

0.414

AC:

62865

AN:

151924

Hom.:

14071

Cov.:

show subpopulations

Gnomad AFR

AF:

0.313

Gnomad AMI

AF:

0.613

Gnomad AMR

AF:

0.315

Gnomad ASJ

AF:

0.382

Gnomad EAS

AF:

0.0840

Gnomad SAS

AF:

0.332

Gnomad FIN

AF:

0.496

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.515

Gnomad OTH

AF:

0.395

GnomAD4 exome

AF:

0.438

AC:

252036

AN:

575724

Hom.:

60406

AF XY:

0.437

AC XY:

137558

AN XY:

315034

show subpopulations

African (AFR)

AF:

0.308

AC:

4903

AN:

15910

American (AMR)

AF:

0.245

AC:

8695

AN:

35434

Ashkenazi Jewish (ASJ)

AF:

0.377

AC:

7309

AN:

19378

East Asian (EAS)

AF:

0.0639

AC:

2171

AN:

33998

South Asian (SAS)

AF:

0.348

AC:

22361

AN:

64264

European-Finnish (FIN)

AF:

0.516

AC:

19975

AN:

38728

Middle Eastern (MID)

AF:

0.397

AC:

958

AN:

2412

European-Non Finnish (NFE)

AF:

0.514

AC:

172163

AN:

335196

Other (OTH)

AF:

0.444

AC:

13501

AN:

30404

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

6239

12477

18716

24954

31193

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

950

1900

2850

3800

4750

<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:

0.413

AC:

62861

AN:

152042

Hom.:

14071

Cov.:

AF XY:

0.405

AC XY:

30048

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.313

AC:

12975

AN:

41470

American (AMR)

AF:

0.314

AC:

4800

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.382

AC:

1324

AN:

3468

East Asian (EAS)

AF:

0.0840

AC:

436

AN:

5190

South Asian (SAS)

AF:

0.333

AC:

1601

AN:

4814

European-Finnish (FIN)

AF:

0.496

AC:

5239

AN:

10568

Middle Eastern (MID)

AF:

0.429

AC:

126

AN:

294

European-Non Finnish (NFE)

AF:

0.515

AC:

34981

AN:

67936

Other (OTH)

AF:

0.389

AC:

822

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1814

3627

5441

7254

9068

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

584

1168

1752

2336

2920

<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:

0.477

Hom.:

8847

Bravo

AF:

0.393

Asia WGS

AF:

0.208

AC:

730

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.79

PhyloP100

3.1

Mutation Taster

=100/0

polymorphism (auto)

(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