Variant chr11-64792268-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_004579.5(MAP4K2):c.1818C>T(p.Asn606Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00148 in 1,609,790 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0013 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0015 ( 11 hom. )

Consequence

MAP4K2
NM_004579.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.66

Variant links:

Genes affected

MAP4K2 (HGNC:6864): (mitogen-activated protein kinase kinase kinase kinase 2) The protein encoded by this gene is a member of the serine/threonine protein kinase family. Although this kinase is found in many tissues, its expression in lymphoid follicles is restricted to the cells of germinal centre, where it may participate in B-cell differentiation. This kinase can be activated by TNF-alpha, and has been shown to specifically activate MAP kinases. This kinase is also found to interact with TNF receptor-associated factor 2 (TRAF2), which is involved in the activation of MAP3K1/MEKK1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

MAP4K2 links:

MAP4K2 (HGNC:):

MAP4K2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 11-64792268-G-A is Benign according to our data. Variant chr11-64792268-G-A is described in ClinVar as [Benign]. Clinvar id is 723318.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.66 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP4K2	NM_004579.5 linkuse as main transcript	c.1818C>T	p.Asn606Asn	synonymous_variant	26/32	ENST00000294066.7	NP_004570.2	Q12851-1A0A024R567
MAP4K2	NM_001307990.2 linkuse as main transcript	c.1794C>T	p.Asn598Asn	synonymous_variant	26/32		NP_001294919.1	Q12851-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP4K2	ENST00000294066.7 linkuse as main transcript	c.1818C>T	p.Asn606Asn	synonymous_variant	26/32	1	NM_004579.5	ENSP00000294066.2		Q12851-1

Frequencies

GnomAD3 genomes

AF:

0.00133

AC:

203

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.0153

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00455

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.0159

Gnomad NFE

AF:

0.00122

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00210

AC:

499

AN:

237230

Hom.:

AF XY:

0.00229

AC XY:

297

AN XY:

129948

show subpopulations

Gnomad AFR exome

AF:

0.000141

Gnomad AMR exome

AF:

0.00106

Gnomad ASJ exome

AF:

0.0166

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00413

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00145

Gnomad OTH exome

AF:

0.00376

GnomAD4 exome

AF:

0.00150

AC:

2185

AN:

1457460

Hom.:

Cov.:

AF XY:

0.00167

AC XY:

1213

AN XY:

724800

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.00115

Gnomad4 ASJ exome

AF:

0.0178

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00404

Gnomad4 FIN exome

AF:

0.0000193

Gnomad4 NFE exome

AF:

0.000947

Gnomad4 OTH exome

AF:

0.00319

GnomAD4 genome

AF:

0.00133

AC:

202

AN:

152330

Hom.:

Cov.:

AF XY:

0.00136

AC XY:

101

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.0153

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00455

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00122

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00275

Hom.:

Bravo

AF:

0.00156

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

9.1

DANN

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over