19-7911242-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_145185.4(MAP2K7):c.856-8C>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,610,038 control chromosomes in the GnomAD database, including 9,781 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.089 (777 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9004 hom.)
• Consequence: MAP2K7 NM_145185.4 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00003761
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.62

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 19-7911242-C-G is Benign according to our data. Variant chr19-7911242-C-G is described in ClinVar as [Benign]. Clinvar id is 1222270.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP2K7	NM_145185.4	c.856-8C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000397979.4
MAP2K7	NM_001297555.2	c.904-8C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
MAP2K7	NM_001297556.2	c.856-8C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
MAP2K7	XM_006722800.3	c.904-8C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP2K7	ENST00000397979.4	c.856-8C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_145185.4	P4

Frequencies

GnomAD3 genomes AF: 0.0886 AC: 13451 AN: 151788 Hom.: 775 Cov.: 32

Gnomad AFR AF: 0.0354

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.0950

Gnomad OTH AF: 0.106

GnomAD3 exomes AF: 0.117 AC: 28665 AN: 245342 Hom.: 1953 AF XY: 0.115 AC XY: 15377 AN XY: 133996

Gnomad AFR exome AF: 0.0330

Gnomad AMR exome AF: 0.152

Gnomad ASJ exome AF: 0.113

Gnomad EAS exome AF: 0.241

Gnomad SAS exome AF: 0.114

Gnomad FIN exome AF: 0.104

Gnomad NFE exome AF: 0.0999

Gnomad OTH exome AF: 0.127

GnomAD4 exome AF: 0.105 AC: 153122 AN: 1458132 Hom.: 9004 Cov.: 36 AF XY: 0.105 AC XY: 76366 AN XY: 725428

Gnomad4 AFR exome AF: 0.0307

Gnomad4 AMR exome AF: 0.151

Gnomad4 ASJ exome AF: 0.113

Gnomad4 EAS exome AF: 0.246

Gnomad4 SAS exome AF: 0.114

Gnomad4 FIN exome AF: 0.109

Gnomad4 NFE exome AF: 0.0986

Gnomad4 OTH exome AF: 0.115

GnomAD4 genome AF: 0.0886 AC: 13466 AN: 151906 Hom.: 777 Cov.: 32 AF XY: 0.0905 AC XY: 6722 AN XY: 74242

Gnomad4 AFR AF: 0.0353

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.235

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.0950

Gnomad4 OTH AF: 0.105

Alfa AF: 0.0251 Hom.: 32

Bravo AF: 0.0896

EpiCase AF: 0.101

EpiControl AF: 0.100

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 28, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.040
Dann	Benign	0.43
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000038
dbscSNV1_RF	Benign	0.036
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs56358830; hg19: chr19-7976127; COSMIC: COSV67607857; COSMIC: COSV67607857;