NM_145160.3:c.849C>T

Variant names:

• chr15-67692480-C-T
• rs55966838
• NM_145160.3:c.849C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_145160.3(MAP2K5):​c.849C>T​(p.Asp283Asp) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 1,612,470 control chromosomes in the GnomAD database, including 122 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 0.0072 (10 hom., cov: 32)
  • Exomes 𝑓: 0.011 (112 hom.)
• Consequence: MAP2K5 NM_145160.3 splice_region, synonymous
• Scores: Splicing: ADA: 0.000004392
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.237
• Publications: 6 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 15-67692480-C-T is Benign according to our data. Variant chr15-67692480-C-T is described in ClinVar as Benign. ClinVar VariationId is 708695.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.237 with no splicing effect.
• BS2: High AC in GnomAd4 at 1096 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.849C>T	p.Asp283Asp	splice_region synonymous	Exon 14 of 22	NP_660143.1	Q13163-1
	MAP2K5	NM_002757.4		c.849C>T	p.Asp283Asp	splice_region synonymous	Exon 14 of 21	NP_002748.1	Q13163-2
	MAP2K5	NM_001206804.2		c.741C>T	p.Asp247Asp	splice_region synonymous	Exon 14 of 22	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.849C>T	p.Asp283Asp	splice_region synonymous	Exon 14 of 22	ENSP00000178640.5	Q13163-1
	MAP2K5	ENST00000395476.6	TSL:1	c.849C>T	p.Asp283Asp	splice_region synonymous	Exon 14 of 21	ENSP00000378859.2	Q13163-2
	MAP2K5	ENST00000952141.1		c.849C>T	p.Asp283Asp	splice_region synonymous	Exon 14 of 24	ENSP00000622200.1

Frequencies

GnomAD3 genomes AF: 0.00720 AC: 1096 AN: 152154 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.00186

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.00785

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.00632

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0116

Gnomad OTH AF: 0.00813

GnomAD2 exomes AF: 0.00718 AC: 1802 AN: 251098 AF XY: 0.00715

Gnomad AFR exome AF: 0.00185

Gnomad AMR exome AF: 0.00426

Gnomad ASJ exome AF: 0.000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00730

Gnomad NFE exome AF: 0.0116

Gnomad OTH exome AF: 0.00685

GnomAD4 exome AF: 0.0109 AC: 15987 AN: 1460198 Hom.: 112 Cov.: 29 AF XY: 0.0106 AC XY: 7698 AN XY: 726516

African (AFR) AF: 0.00162 AC: 54 AN: 33432

American (AMR) AF: 0.00412 AC: 184 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.00130 AC: 34 AN: 26102

East Asian (EAS) AF: 0.0000757 AC: 3 AN: 39652

South Asian (SAS) AF: 0.00386 AC: 333 AN: 86196

European-Finnish (FIN) AF: 0.00736 AC: 393 AN: 53398

Middle Eastern (MID) AF: 0.000695 AC: 4 AN: 5756

European-Non Finnish (NFE) AF: 0.0131 AC: 14540 AN: 1110688

Other (OTH) AF: 0.00733 AC: 442 AN: 60322

GnomAD4 genome AF: 0.00720 AC: 1096 AN: 152272 Hom.: 10 Cov.: 32 AF XY: 0.00747 AC XY: 556 AN XY: 74460

African (AFR) AF: 0.00185 AC: 77 AN: 41556

American (AMR) AF: 0.00784 AC: 120 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00249 AC: 12 AN: 4820

European-Finnish (FIN) AF: 0.00632 AC: 67 AN: 10604

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

European-Non Finnish (NFE) AF: 0.0116 AC: 786 AN: 68014

Other (OTH) AF: 0.00804 AC: 17 AN: 2114

Alfa AF: 0.0100 Hom.: 23

Bravo AF: 0.00680

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.0114

EpiControl AF: 0.0105

ClinVar

ClinVar submissions

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	-0.62
CADD	Benign	5.9
DANN	Benign	0.43
PhyloP100		0.24
Mutation Taster		=72/28	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0000044
dbscSNV1_RF	Benign	0.0
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: rs55966838; hg19: chr15-67984818; COSMIC: COSV51613937;