2-101823704-G-A

Position:

• chr2-101823704-G-A

Variant summary

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

The NM_001395002.1(MAP4K4):​c.181-224G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 151,954 control chromosomes in the GnomAD database, including 6,552 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.27 (6552 hom., cov: 31)
• Consequence: MAP4K4 NM_001395002.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.91

Genes affected

MAP4K4 (HGNC:6866): (mitogen-activated protein kinase kinase kinase kinase 4) The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase has been shown to specifically activate MAPK8/JNK. The activation of MAPK8 by this kinase is found to be inhibited by the dominant-negative mutants of MAP3K7/TAK1, MAP2K4/MKK4, and MAP2K7/MKK7, which suggests that this kinase may function through the MAP3K7-MAP2K4-MAP2K7 kinase cascade, and mediate the TNF-alpha signaling pathway. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 2-101823704-G-A is Benign according to our data. Variant chr2-101823704-G-A is described in ClinVar as [Benign]. Clinvar id is 1269539.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP4K4	NM_001395002.1	c.181-224G>A		intron_variant		ENST00000324219.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP4K4	ENST00000324219.9	c.181-224G>A		intron_variant		5	NM_001395002.1	P3

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41656 AN: 151836 Hom.: 6546 Cov.: 31

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.290

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.274 AC: 41654 AN: 151954 Hom.: 6552 Cov.: 31 AF XY: 0.278 AC XY: 20618 AN XY: 74254

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.400

Gnomad4 EAS AF: 0.468

Gnomad4 SAS AF: 0.484

Gnomad4 FIN AF: 0.283

Gnomad4 NFE AF: 0.325

Gnomad4 OTH AF: 0.297

Alfa AF: 0.315 Hom.: 8684

Bravo AF: 0.264

Asia WGS AF: 0.498 AC: 1729 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

GeneDx

May 13, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.082
DANN	Benign	0.81

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

LitVar

Other links and lift over

dbSNP: rs2286240; hg19: chr2-102440166;