rs762647820

Variant names:

• chr15-67806709-C-A
• rs762647820
• NM_145160.3:c.1306C>A

Your query was ambiguous. Multiple possible variants found:

• chr15-67806709-C-A
• chr15-67806709-C-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_145160.3(MAP2K5):​c.1306C>A​(p.Arg436Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MAP2K5 NM_145160.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.590
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP7: Synonymous conserved (PhyloP=0.59 with no splicing effect.

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.1306C>A	p.Arg436Arg	synonymous	Exon 22 of 22	NP_660143.1	Q13163-1
	MAP2K5	NM_002757.4		c.1276C>A	p.Arg426Arg	synonymous	Exon 21 of 21	NP_002748.1	Q13163-2
	MAP2K5	NM_001206804.2		c.1198C>A	p.Arg400Arg	synonymous	Exon 22 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.1306C>A	p.Arg436Arg	synonymous	Exon 22 of 22	ENSP00000178640.5	Q13163-1
	MAP2K5	ENST00000395476.6	TSL:1	c.1276C>A	p.Arg426Arg	synonymous	Exon 21 of 21	ENSP00000378859.2	Q13163-2
	MAP2K5	ENST00000952141.1		c.1477C>A	p.Arg493Arg	synonymous	Exon 24 of 24	ENSP00000622200.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1399752 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 690660

African (AFR) AF: 0.00 AC: 0 AN: 31712

American (AMR) AF: 0.00 AC: 0 AN: 35936

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25192

East Asian (EAS) AF: 0.00 AC: 0 AN: 35894

South Asian (SAS) AF: 0.00 AC: 0 AN: 79350

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47890

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5702

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1079984

Other (OTH) AF: 0.00 AC: 0 AN: 58092

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	6.9
DANN	Benign	0.54
PhyloP100		0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs762647820; hg19: chr15-68099047;