rs55709438

Positions:

• chr15-67569020-C-A
• chr15-67569020-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145160.3(MAP2K5):​c.252+5670C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 110,576 control chromosomes in the GnomAD database, including 1,951 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 0.19 (1951 hom., cov: 26)
• Consequence: MAP2K5 NM_145160.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.306

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP2K5	NM_145160.3	c.252+5670C>A		intron_variant		ENST00000178640.10	NP_660143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP2K5	ENST00000178640.10	c.252+5670C>A		intron_variant		1	NM_145160.3	ENSP00000178640	P1

Frequencies

GnomAD3 genomes AF: 0.189 AC: 20880 AN: 110588 Hom.: 1947 Cov.: 26

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.0875

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.0826

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.166

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.189 AC: 20887 AN: 110576 Hom.: 1951 Cov.: 26 AF XY: 0.191 AC XY: 10043 AN XY: 52614

Gnomad4 AFR AF: 0.318

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.0875

Gnomad4 EAS AF: 0.242

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.165

Alfa AF: 0.00253 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.23
DANN	Benign	0.44

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

Other links and lift over

dbSNP: rs55709438; hg19: chr15-67861358; COSMIC: COSV51610284;