chr12-54402202-G-A

Position:

• chr12-54402202-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002205.5(ITGA5):​c.2111C>T​(p.Ser704Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ITGA5 NM_002205.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.863

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]

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

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26747185).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGA5	NM_002205.5	c.2111C>T	p.Ser704Leu	missense_variant	20/30	ENST00000293379.9
GPR84-AS1	NR_120486.1	n.207-5195G>A		intron_variant, non_coding_transcript_variant
ITGA5	XM_024448970.2	c.599C>T	p.Ser200Leu	missense_variant	7/17
GPR84-AS1	NR_120487.1	n.207-5195G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGA5	ENST00000293379.9	c.2111C>T	p.Ser704Leu	missense_variant	20/30	1	NM_002205.5	P1
GPR84-AS1	ENST00000550474.5	n.48-25655G>A		intron_variant, non_coding_transcript_variant		4
GPR84-AS1	ENST00000552785.1	n.106-5195G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 27, 2023

The c.2111C>T (p.S704L) alteration is located in exon 20 (coding exon 20) of the ITGA5 gene. This alteration results from a C to T substitution at nucleotide position 2111, causing the serine (S) at amino acid position 704 to be replaced by a leucine (L). 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	Benign	0.19
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Benign	0.065
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.76	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	0.13	N
REVEL	Benign	0.19
Sift	Benign	0.17	T
Sift4G	Benign	0.32	T
Polyphen		0.47	P
Vest4		0.49
MutPred		0.54		Loss of glycosylation at S704 (P = 0.0053);
MVP		0.83
MPC		0.34
ClinPred		0.98	D
GERP RS		4.3
Varity_R		0.26
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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.

Other links and lift over

hg19: chr12-54795986;