NM_002207.3:c.2668G>C

Variant names:

• chr3-37779902-G-C
• NM_002207.3:c.2668G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_002207.3(ITGA9):​c.2668G>C​(p.Asp890His) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ITGA9 NM_002207.3 missense, splice_region
• Scores: Splicing: ADA: 0.9997
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.81
• Publications: 0 publications found

Genes affected

ITGA9 (HGNC:6145): (integrin subunit alpha 9) This gene encodes an alpha integrin. Integrins are heterodimeric integral membrane glycoproteins composed of an alpha chain and a beta chain that mediate cell-cell and cell-matrix adhesion. The protein encoded by this gene, when bound to the beta 1 chain, forms an integrin that is a receptor for VCAM1, cytotactin and osteopontin. Expression of this gene has been found to be upregulated in small cell lung cancers. [provided by RefSeq, Jul 2008]

ITGA9-AS1 (HGNC:49668): (ITGA9 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002207.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA9	NM_002207.3	MANE Select	c.2668G>C	p.Asp890His	missense splice_region	Exon 25 of 28	NP_002198.2
	ITGA9-AS1	NR_110531.1		n.257-25850C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA9	ENST00000264741.10	TSL:1 MANE Select	c.2668G>C	p.Asp890His	missense splice_region	Exon 25 of 28	ENSP00000264741.5	Q13797
	ITGA9	ENST00000921363.1		c.2665G>C	p.Asp889His	missense splice_region	Exon 25 of 28	ENSP00000591422.1
	ITGA9	ENST00000944256.1		c.2665G>C	p.Asp889His	missense splice_region	Exon 25 of 28	ENSP00000614315.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.030	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		8.8
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.19
Sift	Benign	0.55	T
Sift4G	Benign	0.47	T
Polyphen		0.95	P
Vest4		0.87
MutPred		0.52		Loss of ubiquitination at K893 (P = 0.0256)
MVP		0.67
MPC		0.84
ClinPred		0.90	D
GERP RS		5.8
PromoterAI		-0.0098	Neutral
Varity_R		0.43
gMVP		0.72
Mutation Taster		=16/84	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.96
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr3-37821393;