MAP4K2 p.Ala806Ala

Variant names:

• chr11-64789581-G-G
• NM_004579.5:c.

Your query was ambiguous. Multiple possible variants found:

• chr11-64789582--
• chr11-64789582-C-A
• chr11-64789582-C-G
• chr11-64789582-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004579.5(MAP4K2):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MAP4K2 NM_004579.5 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.80
• Publications: 0 publications found

Genes affected

MAP4K2 (HGNC:6864): (mitogen-activated protein kinase kinase kinase kinase 2) The protein encoded by this gene is a member of the serine/threonine protein kinase family. Although this kinase is found in many tissues, its expression in lymphoid follicles is restricted to the cells of germinal centre, where it may participate in B-cell differentiation. This kinase can be activated by TNF-alpha, and has been shown to specifically activate MAP kinases. This kinase is also found to interact with TNF receptor-associated factor 2 (TRAF2), which is involved in the activation of MAP3K1/MEKK1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004579.5. 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
	MAP4K2	NM_004579.5	MANE Select	c.		exon_region	Exon 32 of 32	NP_004570.2
	MAP4K2	NM_001307990.2		c.		exon_region	Exon 32 of 32	NP_001294919.1	Q12851-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP4K2	ENST00000294066.7	TSL:1 MANE Select	c.		exon_region	Exon 32 of 32	ENSP00000294066.2	Q12851-1
	MAP4K2	ENST00000377350.7	TSL:1	c.		exon_region	Exon 32 of 32	ENSP00000366567.3	Q12851-2
	MAP4K2	ENST00000944408.1		c.		exon_region	Exon 32 of 32	ENSP00000614467.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-2.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-64557053;