Variant 7-139376080-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016019.5(LUC7L2):c.80G>A(p.Arg27Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,130 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

LUC7L2
NM_016019.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.97

Variant links:

Genes affected

LUC7L2 (HGNC:21608): (LUC7 like 2, pre-mRNA splicing factor) This gene encodes a protein that contains a C2H2-type zinc finger, coiled-coil region and arginine, serine-rich (RS) domain. A similar protein in mouse interacts with sodium channel modifier 1, and the encoded protein may be involved in the recognition of non-consensus splice donor sites in association with the U1 snRNP spliceosomal subunit. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Sep 2011]

LUC7L2 links:

FMC1-LUC7L2 (HGNC:44671): (FMC1-LUC7L2 readthrough) This locus represents naturally occurring readthrough transcription between the neighboring C7orf55 (chromosome 7 open reading frame 55) and LUC7L2 (LUC7-like 2) genes on chromosome 7. The readthrough transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Jul 2012]

FMC1-LUC7L2 links:

LUC7L2 (HGNC:):

LUC7L2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LUC7L2	NM_016019.5 linkuse as main transcript	c.80G>A	p.Arg27Gln	missense_variant	2/10	ENST00000354926.9	NP_057103.2	Q9Y383-1
FMC1-LUC7L2	NM_001244584.3 linkuse as main transcript	c.278G>A	p.Arg93Gln	missense_variant	3/11		NP_001231513.1	Q96HJ9-2A0A0A6YYJ8
LUC7L2	NM_001270643.2 linkuse as main transcript	c.77G>A	p.Arg26Gln	missense_variant	3/11		NP_001257572.1	Q9Y383-2
LUC7L2	NM_001244585.2 linkuse as main transcript	c.71G>A	p.Arg24Gln	missense_variant	3/11		NP_001231514.1	Q9Y383-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LUC7L2	ENST00000354926.9 linkuse as main transcript	c.80G>A	p.Arg27Gln	missense_variant	2/10	1	NM_016019.5	ENSP00000347005.4		Q9Y383-1
FMC1-LUC7L2	ENST00000541515.3 linkuse as main transcript	c.278G>A	p.Arg93Gln	missense_variant	3/11	2		ENSP00000440222.1		A0A0A6YYJ8

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152130

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152130

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 28, 2024

The c.80G>A (p.R27Q) alteration is located in exon 2 (coding exon 2) of the LUC7L2 gene. This alteration results from a G to A substitution at nucleotide position 80, causing the arginine (R) at amino acid position 27 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Uncertain

0.063

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.012

.;.;T;.;.

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

.;D;D;D;D

M_CAP

Benign

0.043

MetaRNN

Uncertain

0.49

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

.;.;L;.;.

PROVEAN

Benign

-0.67

N;.;N;N;N

REVEL

Uncertain

0.34

Sift

Benign

0.27

T;.;T;D;T

Sift4G

Benign

0.77

T;T;T;T;T

Polyphen

0.74, 0.47

.;P;P;.;.

Vest4

0.69

MutPred

0.37

.;.;Loss of MoRF binding (P = 0.0313);.;.;

MVP

0.37

MPC

1.7, 1.8

ClinPred

0.90

GERP RS

6.0

Varity_R

0.26

gMVP

0.70

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