Variant chr8-55941981-A-G 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.122A>G(p.Gln41Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,296 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: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

LYN
NM_002350.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.17

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=0.1290519).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
LYN	NM_002350.4 linkuse as main transcript	c.122A>G	p.Gln41Arg	missense_variant	2/13	ENST00000519728.6
LYN	NM_001111097.3 linkuse as main transcript	c.69+53A>G		intron_variant
LYN	XM_011517529.4 linkuse as main transcript	c.-135-4467A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LYN	ENST00000519728.6 linkuse as main transcript	c.122A>G	p.Gln41Arg	missense_variant	2/13	1	NM_002350.4	P4	P07948-1
LYN	ENST00000520220.6 linkuse as main transcript	c.69+53A>G		intron_variant		1		A1	P07948-2
LYN	ENST00000520050.1 linkuse as main transcript	c.122A>G	p.Gln41Arg	missense_variant	2/6	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461296

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726954

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Oct 14, 2023

This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 41 of the LYN protein (p.Gln41Arg). This variant is not present in population databases (gnomAD no frequency). 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

0.12

BayesDel_addAF

Benign

-0.012

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.32

T;.

Eigen

Benign

-0.18

Eigen_PC

Benign

0.052

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.59

T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.2

L;.

MutationTaster

Benign

1.0

D;N

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.43

N;N

REVEL

Benign

0.062

Sift

Benign

0.30

T;T

Sift4G

Benign

0.52

T;T

Polyphen

0.012

B;.

Vest4

0.17

MutPred

0.15

Gain of MoRF binding (P = 0.0401);Gain of MoRF binding (P = 0.0401);

MVP

0.84

MPC

1.1

ClinPred

0.27

GERP RS

6.0

Varity_R

0.074

gMVP

0.43

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over