rs12905175

chr15-67796566-C-T

Variant summary

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

The NM_145160.3(MAP2K5):c.1243-10080C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0395 in 152,274 control chromosomes in the GnomAD database, including 203 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 0.040 (203 hom., cov: 33)
• Consequence: MAP2K5 NM_145160.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.431

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP2K5	NM_145160.3	c.1243-10080C>T		intron_variant		ENST00000178640.10
MAP2K5	NM_001206804.2	c.1135-10080C>T		intron_variant
MAP2K5	NM_002757.4	c.1213-10080C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP2K5	ENST00000178640.10	c.1243-10080C>T		intron_variant		1	NM_145160.3	P1

Frequencies

GnomAD3 genomes AF: 0.0396 AC: 6022 AN: 152156 Hom.: 203 Cov.: 33

Gnomad AFR AF: 0.0113

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.0210

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.000961

Gnomad SAS AF: 0.0502

Gnomad FIN AF: 0.0466

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0631

Gnomad OTH AF: 0.0253

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

GnomAD4 genome AF: 0.0395 AC: 6016 AN: 152274 Hom.: 203 Cov.: 33 AF XY: 0.0377 AC XY: 2807 AN XY: 74458

Gnomad4 AFR AF: 0.0113

Gnomad4 AMR AF: 0.0209

Gnomad4 ASJ AF: 0.0138

Gnomad4 EAS AF: 0.000963

Gnomad4 SAS AF: 0.0499

Gnomad4 FIN AF: 0.0466

Gnomad4 NFE AF: 0.0631

Gnomad4 OTH AF: 0.0246

Alfa AF: 0.0534 Hom.: 124

Bravo AF: 0.0342

Asia WGS AF: 0.0130 AC: 44 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.3
Dann	Benign	0.85

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: rs12905175; hg19: chr15-68088904;