chr15-67779937-C-T

Variant names:

• chr15-67779937-C-T
• rs3784709
• NM_145160.3:c.1242+7185C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145160.3(MAP2K5):​c.1242+7185C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 151,978 control chromosomes in the GnomAD database, including 11,014 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 0.37 (11014 hom., cov: 32)
• Consequence: MAP2K5 NM_145160.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.514
• Publications: 14 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP2K5	NM_145160.3	MANE Select	c.1242+7185C>T		intron	N/A	NP_660143.1
	MAP2K5	NM_002757.4		c.1212+7185C>T		intron	N/A	NP_002748.1
	MAP2K5	NM_001206804.2		c.1134+7185C>T		intron	N/A	NP_001193733.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP2K5	ENST00000178640.10	TSL:1 MANE Select	c.1242+7185C>T		intron	N/A	ENSP00000178640.5
	MAP2K5	ENST00000395476.6	TSL:1	c.1212+7185C>T		intron	N/A	ENSP00000378859.2
	MAP2K5	ENST00000354498.9	TSL:2	c.1134+7185C>T		intron	N/A	ENSP00000346493.5

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55711 AN: 151860 Hom.: 10972 Cov.: 32

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.384

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

GnomAD4 genome AF: 0.367 AC: 55804 AN: 151978 Hom.: 11014 Cov.: 32 AF XY: 0.373 AC XY: 27723 AN XY: 74298

African (AFR) AF: 0.357 AC: 14779 AN: 41428

American (AMR) AF: 0.530 AC: 8091 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 1521 AN: 3472

East Asian (EAS) AF: 0.690 AC: 3571 AN: 5172

South Asian (SAS) AF: 0.434 AC: 2087 AN: 4804

European-Finnish (FIN) AF: 0.303 AC: 3209 AN: 10580

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.316 AC: 21452 AN: 67944

Other (OTH) AF: 0.389 AC: 821 AN: 2108

Alfa AF: 0.349 Hom.: 17058

Bravo AF: 0.388

Asia WGS AF: 0.584 AC: 2030 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.91
DANN	Benign	0.40
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3784709; hg19: chr15-68072275;