rs41305272

Positions:

• chr15-67807105-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000178640.10(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 ENST00000178640.10 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42

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=-0.51).
• 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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3625 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP2K5	NM_145160.3	c.*355C>T		3_prime_UTR_variant	22/22	ENST00000178640.10	NP_660143.1
MAP2K5	NM_001206804.2	c.*355C>T		3_prime_UTR_variant	22/22		NP_001193733.1
MAP2K5	NM_002757.4	c.*355C>T		3_prime_UTR_variant	21/21		NP_002748.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP2K5	ENST00000178640.10	c.*355C>T		3_prime_UTR_variant	22/22	1	NM_145160.3	ENSP00000178640	P1

Frequencies

GnomAD3 genomes AF: 0.0238 AC: 3627 AN: 152212 Hom.: 59 Cov.: 33

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.: 7 AF XY: 0.0333 AC XY: 7119 AN XY: 213960

Gnomad4 AFR exome AF: 0.00507

Gnomad4 AMR exome AF: 0.0168

Gnomad4 ASJ exome AF: 0.0179

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00822

Gnomad4 FIN exome AF: 0.0169

Gnomad4 NFE exome AF: 0.0429

Gnomad4 OTH exome AF: 0.0327

GnomAD4 genome AF: 0.0238 AC: 3625 AN: 152330 Hom.: 58 Cov.: 33 AF XY: 0.0222 AC XY: 1651 AN XY: 74490

Gnomad4 AFR AF: 0.00734

Gnomad4 AMR AF: 0.0165

Gnomad4 ASJ AF: 0.0205

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00580

Gnomad4 FIN AF: 0.0108

Gnomad4 NFE AF: 0.0401

Gnomad4 OTH AF: 0.0175

Alfa AF: 0.0328 Hom.: 37

Bravo AF: 0.0236

Asia WGS AF: 0.00577 AC: 20 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
DANN	Benign	0.78

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: rs41305272; hg19: chr15-68099443;