19-7909830-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145185.4(MAP2K7):c.200C>T(p.Pro67Leu) variant causes a missense 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MAP2K7 NM_145185.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.39

Genes affected

MAP2K7 (HGNC:6847): (mitogen-activated protein kinase kinase 7) The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase specifically activates MAPK8/JNK1 and MAPK9/JNK2, and this kinase itself is phosphorylated and activated by MAP kinase kinase kinases including MAP3K1/MEKK1, MAP3K2/MEKK2,MAP3K3/MEKK5, and MAP4K2/GCK. This kinase is involved in the signal transduction mediating the cell responses to proinflammatory cytokines, and environmental stresses. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.096440196).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP2K7	NM_145185.4	c.200C>T	p.Pro67Leu	missense_variant	2/11	ENST00000397979.4
MAP2K7	NM_001297555.2	c.248C>T	p.Pro83Leu	missense_variant	3/12
MAP2K7	NM_001297556.2	c.200C>T	p.Pro67Leu	missense_variant	2/11
MAP2K7	XM_006722800.3	c.248C>T	p.Pro83Leu	missense_variant	3/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP2K7	ENST00000397979.4	c.200C>T	p.Pro67Leu	missense_variant	2/11	1	NM_145185.4	P4
MAP2K7	ENST00000397983.7	c.248C>T	p.Pro83Leu	missense_variant	3/12	1		A1
MAP2K7	ENST00000397981.7	c.200C>T	p.Pro67Leu	missense_variant	2/11	1
MAP2K7	ENST00000468058.1	n.265C>T		non_coding_transcript_exon_variant	2/10	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1389122 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 685174

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 08, 2022

The c.200C>T (p.P67L) alteration is located in exon 2 (coding exon 2) of the MAP2K7 gene. This alteration results from a C to T substitution at nucleotide position 200, causing the proline (P) at amino acid position 67 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
Cadd	Benign	21
Dann	Uncertain	0.99
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.29	N
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.096	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.34	N;.;N
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.86	N;N;N
REVEL	Benign	0.076
Sift	Benign	0.38	T;T;T
Sift4G	Benign	0.59	T;T;T
Polyphen		0.0	B;.;B
Vest4		0.15
MutPred		0.22		Loss of glycosylation at P67 (P = 0.0142);.;Loss of glycosylation at P67 (P = 0.0142);
MVP		0.32
MPC		0.62
ClinPred		0.41	T
GERP RS		5.0
Varity_R		0.076
gMVP		0.35

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-7974715;