chr19-7911169-G-C

Position:

• chr19-7911169-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_145185.4(MAP2K7):​c.855+10G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00584 in 1,608,770 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0046 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0060 (37 hom.)
• Consequence: MAP2K7 NM_145185.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.272

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 19-7911169-G-C is Benign according to our data. Variant chr19-7911169-G-C is described in ClinVar as [Benign]. Clinvar id is 777052.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 703 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP2K7	NM_145185.4	c.855+10G>C		intron_variant		ENST00000397979.4
MAP2K7	NM_001297555.2	c.903+10G>C		intron_variant
MAP2K7	NM_001297556.2	c.855+10G>C		intron_variant
MAP2K7	XM_006722800.3	c.903+10G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP2K7	ENST00000397979.4	c.855+10G>C		intron_variant		1	NM_145185.4	P4

Frequencies

GnomAD3 genomes AF: 0.00464 AC: 705 AN: 152086 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00393

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00311

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00777

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00481 AC: 1133 AN: 235744 Hom.: 8 AF XY: 0.00480 AC XY: 626 AN XY: 130342

Gnomad AFR exome AF: 0.00102

Gnomad AMR exome AF: 0.00438

Gnomad ASJ exome AF: 0.00239

Gnomad EAS exome AF: 0.000114

Gnomad SAS exome AF: 0.000956

Gnomad FIN exome AF: 0.00303

Gnomad NFE exome AF: 0.00784

Gnomad OTH exome AF: 0.00690

GnomAD4 exome AF: 0.00597 AC: 8697 AN: 1456566 Hom.: 37 Cov.: 37 AF XY: 0.00588 AC XY: 4259 AN XY: 723988

Gnomad4 AFR exome AF: 0.000928

Gnomad4 AMR exome AF: 0.00440

Gnomad4 ASJ exome AF: 0.00234

Gnomad4 EAS exome AF: 0.0000757

Gnomad4 SAS exome AF: 0.00115

Gnomad4 FIN exome AF: 0.00349

Gnomad4 NFE exome AF: 0.00705

Gnomad4 OTH exome AF: 0.00464

GnomAD4 genome AF: 0.00462 AC: 703 AN: 152204 Hom.: 3 Cov.: 33 AF XY: 0.00425 AC XY: 316 AN XY: 74406

Gnomad4 AFR AF: 0.00147

Gnomad4 AMR AF: 0.00392

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00311

Gnomad4 NFE AF: 0.00777

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00248 Hom.: 1

Bravo AF: 0.00473

Asia WGS AF: 0.00115 AC: 4 AN: 3478

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

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	12
DANN	Benign	0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs200132456; hg19: chr19-7976054;