19-7909785-G-T

Position:

• chr19-7909785-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_145185.4(MAP2K7):​c.155G>T​(p.Gly52Val) 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. 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: 1.66

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33348587).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP2K7	NM_145185.4	c.155G>T	p.Gly52Val	missense_variant	2/11	ENST00000397979.4	NP_660186.1
MAP2K7	NM_001297555.2	c.203G>T	p.Gly68Val	missense_variant	3/12		NP_001284484.1
MAP2K7	NM_001297556.2	c.155G>T	p.Gly52Val	missense_variant	2/11		NP_001284485.1
MAP2K7	XM_006722800.3	c.203G>T	p.Gly68Val	missense_variant	3/12		XP_006722863.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP2K7	ENST00000397979.4	c.155G>T	p.Gly52Val	missense_variant	2/11	1	NM_145185.4	ENSP00000381066	P4
MAP2K7	ENST00000397983.7	c.203G>T	p.Gly68Val	missense_variant	3/12	1		ENSP00000381070	A1
MAP2K7	ENST00000397981.7	c.155G>T	p.Gly52Val	missense_variant	2/11	1		ENSP00000381068
MAP2K7	ENST00000468058.1	n.220G>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: 1390496 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 686056

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

Dec 01, 2022

The c.155G>T (p.G52V) alteration is located in exon 2 (coding exon 2) of the MAP2K7 gene. This alteration results from a G to T substitution at nucleotide position 155, causing the glycine (G) at amino acid position 52 to be replaced by a valine (V). 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	0.084
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.49	.;.;T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.33	T;T;T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	1.5	L;.;L
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-3.9	D;D;D
REVEL	Benign	0.28
Sift	Uncertain	0.0050	D;D;D
Sift4G	Benign	0.094	T;T;T
Polyphen		0.97	D;.;P
Vest4		0.38
MutPred		0.23		Loss of relative solvent accessibility (P = 0.0306);.;Loss of relative solvent accessibility (P = 0.0306);
MVP		0.63
MPC		0.82
ClinPred		0.90	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.34
gMVP		0.39

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: chr19-7974670;