16-30499211-A-C

Variant names:

• chr16-30499211-A-C
• NM_002209.3:c.1970A>C

Variant summary

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

The NM_002209.3(ITGAL):​c.1970A>C​(p.Lys657Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ITGAL NM_002209.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.26

Genes affected

ITGAL (HGNC:6148): (integrin subunit alpha L) ITGAL encodes the integrin alpha L chain. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. This I-domain containing alpha integrin combines with the beta 2 chain (ITGB2) to form the integrin lymphocyte function-associated antigen-1 (LFA-1), which is expressed on all leukocytes. LFA-1 plays a central role in leukocyte intercellular adhesion through interactions with its ligands, ICAMs 1-3 (intercellular adhesion molecules 1 through 3), and also functions in lymphocyte costimulatory signaling. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ENSG00000261332 (HGNC:56737): (ITGAL antisense RNA 1)

ACMG classification

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 rank	MANE	Protein	UniProt
ITGAL	NM_002209.3	c.1970A>C	p.Lys657Thr	missense_variant	Exon 16 of 31	ENST00000356798.11	NP_002200.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGAL	ENST00000356798.11	c.1970A>C	p.Lys657Thr	missense_variant	Exon 16 of 31	1	NM_002209.3	ENSP00000349252.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 20, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1970A>C (p.K657T) alteration is located in exon 16 (coding exon 16) of the ITGAL gene. This alteration results from a A to C substitution at nucleotide position 1970, causing the lysine (K) at amino acid position 657 to be replaced by a threonine (T). 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	0.13
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
DANN	Benign	0.93
DEOGEN2	Benign	0.18	T;.;T
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.18
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.84	T;T;T
M_CAP	Benign	0.074	D
MetaRNN	Uncertain	0.43	T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.8	M;.;.
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.3	D;D;N
REVEL	Benign	0.20
Sift	Uncertain	0.023	D;D;T
Sift4G	Benign	0.22	T;D;D
Polyphen		0.40	B;.;D
Vest4		0.41
MutPred		0.60		Loss of ubiquitination at K657 (P = 0.021);.;.;
MVP		0.74
MPC		0.40
ClinPred		0.81	D
GERP RS		4.9
Varity_R		0.32
gMVP		0.58

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.

Other links and lift over

hg19: chr16-30510532;