Variant chr8-55941882-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_002350.4(LYN):c.23G>A(p.Gly8Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Consequence

LYN
NM_002350.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.16

Variant links:

Genes affected

LYN (HGNC:6735): (LYN proto-oncogene, Src family tyrosine kinase) This gene encodes a tyrosine protein kinase, which maybe involved in the regulation of mast cell degranulation, and erythroid differentiation. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2011]

LYN links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), LYN. . Gene score misZ 3.3381 (greater than the threshold 3.09). Trascript score misZ 3.9896 (greater than threshold 3.09). GenCC has associacion of gene with autoinflammatory disease, systemic, with vasculitis.

BP4

Computational evidence support a benign effect (MetaRNN=0.101602644).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
LYN	NM_002350.4 linkuse as main transcript	c.23G>A	p.Gly8Glu	missense_variant	2/13	ENST00000519728.6
LYN	NM_001111097.3 linkuse as main transcript	c.23G>A	p.Gly8Glu	missense_variant	2/13
LYN	XM_011517529.4 linkuse as main transcript	c.-135-4566G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LYN	ENST00000519728.6 linkuse as main transcript	c.23G>A	p.Gly8Glu	missense_variant	2/13	1	NM_002350.4	P4	P07948-1
LYN	ENST00000520220.6 linkuse as main transcript	c.23G>A	p.Gly8Glu	missense_variant	2/13	1		A1	P07948-2
LYN	ENST00000520050.1 linkuse as main transcript	c.23G>A	p.Gly8Glu	missense_variant	2/6	4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152132

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 12, 2024

This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 8 of the LYN protein (p.Gly8Glu). This variant is present in population databases (no rsID available, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with LYN-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

0.0057

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Benign

0.52

DEOGEN2

Benign

0.24

T;.;.

Eigen

Benign

-0.25

Eigen_PC

Benign

0.020

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.72

T;T;T

M_CAP

Benign

0.0074

MetaRNN

Benign

0.10

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;N;.

MutationTaster

Benign

0.89

N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

1.4

N;N;N

REVEL

Benign

0.18

Sift

Benign

0.96

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.27

MutPred

0.23

Gain of ubiquitination at K7 (P = 0.0359);Gain of ubiquitination at K7 (P = 0.0359);Gain of ubiquitination at K7 (P = 0.0359);

MVP

0.64

MPC

1.3

ClinPred

0.78

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.21

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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