Genetic Variant ITGA5:p.Arg585Lys (chr12-54403647-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002205.5(ITGA5):c.1754G>A(p.Arg585Lys) 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 1,461,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R585I) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ITGA5
NM_002205.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.769

Variant links:

Genes affected

ITGA5 (HGNC:6141): (integrin subunit alpha 5) The product of this gene belongs to the integrin alpha chain family. Integrins are heterodimeric integral membrane proteins composed of an alpha subunit and a beta subunit that function in cell surface adhesion and signaling. The encoded preproprotein is proteolytically processed to generate light and heavy chains that comprise the alpha 5 subunit. This subunit associates with the beta 1 subunit to form a fibronectin receptor. This integrin may promote tumor invasion, and higher expression of this gene may be correlated with shorter survival time in lung cancer patients. Note that the integrin alpha 5 and integrin alpha V subunits are encoded by distinct genes. [provided by RefSeq, Oct 2015]

ITGA5 links:

GPR84-AS1 (HGNC:):

GPR84-AS1 links:

GPR84-AS1 (HGNC:56187): (GPR84, ZNF385A, ITGA5 and GTSF1 antisense RNA 1)

GPR84-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.094585806).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA5	NM_002205.5 link	c.1754G>A	p.Arg585Lys	missense_variant	Exon 17 of 30	ENST00000293379.9	NP_002196.4	P08648B2R627
ITGA5	XM_024448970.2 link	c.242G>A	p.Arg81Lys	missense_variant	Exon 4 of 17		XP_024304738.1
GPR84-AS1	NR_120486.1 link	n.207-3750C>T		intron_variant	Intron 1 of 3
GPR84-AS1	NR_120487.1 link	n.207-3750C>T		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA5	ENST00000293379.9 link	c.1754G>A	p.Arg585Lys	missense_variant	Exon 17 of 30	1	NM_002205.5	ENSP00000293379.4		P08648

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461766

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.11

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.76

M_CAP

Benign

0.0055

MetaRNN

Benign

0.095

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.45

REVEL

Benign

0.047

Sift

Benign

0.33

Sift4G

Benign

0.84

Polyphen

0.015

Vest4

0.17

MutPred

0.50

Gain of ubiquitination at R585 (P = 0.0219);

MVP

0.50

MPC

0.36

ClinPred

0.91

GERP RS

3.3

Varity_R

0.29

gMVP

0.40

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

Computational scores

Splicing

Publications

Other links and lift over