rs146184165

Variant names:

• chr15-67550089-C-T
• rs146184165
• NM_145160.3:c.184+7C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_145160.3(MAP2K5):​c.184+7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000507 in 1,612,488 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00024 (0 hom.)
• Consequence: MAP2K5 NM_145160.3 splice_region, intron
• Scores: Splicing: ADA: 0.0009695
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.652
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 15-67550089-C-T is Benign according to our data. Variant chr15-67550089-C-T is described in ClinVar as Benign. ClinVar VariationId is 733231.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 465 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145160.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP2K5	NM_145160.3	MANE Select	c.184+7C>T		splice_region intron	N/A	NP_660143.1	Q13163-1
	MAP2K5	NM_002757.4		c.184+7C>T		splice_region intron	N/A	NP_002748.1	Q13163-2
	MAP2K5	NM_001206804.2		c.76+7C>T		splice_region intron	N/A	NP_001193733.1	Q13163-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP2K5	ENST00000178640.10	TSL:1 MANE Select	c.184+7C>T		splice_region intron	N/A	ENSP00000178640.5	Q13163-1
	MAP2K5	ENST00000395476.6	TSL:1	c.184+7C>T		splice_region intron	N/A	ENSP00000378859.2	Q13163-2
	MAP2K5	ENST00000952141.1		c.184+7C>T		splice_region intron	N/A	ENSP00000622200.1

Frequencies

GnomAD3 genomes AF: 0.00306 AC: 465 AN: 152194 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0108

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00288

GnomAD2 exomes AF: 0.000692 AC: 174 AN: 251396 AF XY: 0.000456

Gnomad AFR exome AF: 0.00972

Gnomad AMR exome AF: 0.000463

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000241 AC: 352 AN: 1460176 Hom.: 0 Cov.: 29 AF XY: 0.000178 AC XY: 129 AN XY: 726466

African (AFR) AF: 0.00891 AC: 298 AN: 33446

American (AMR) AF: 0.000447 AC: 20 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39644

South Asian (SAS) AF: 0.00 AC: 0 AN: 86192

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5764

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1110598

Other (OTH) AF: 0.000481 AC: 29 AN: 60322

GnomAD4 genome AF: 0.00305 AC: 465 AN: 152312 Hom.: 1 Cov.: 33 AF XY: 0.00305 AC XY: 227 AN XY: 74476

African (AFR) AF: 0.0107 AC: 446 AN: 41558

American (AMR) AF: 0.000850 AC: 13 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00285 AC: 6 AN: 2108

Alfa AF: 0.00231 Hom.: 1

Bravo AF: 0.00332

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	11
DANN	Benign	0.57
PhyloP100		0.65
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00097
dbscSNV1_RF	Benign	0.16
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

Other links and lift over

dbSNP: rs146184165; hg19: chr15-67842427;