NM_005353.3:c.2836A>C

Variant names:

• chr16-31423169-A-C
• rs193921125
• NM_005353.3:c.2836A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005353.3(ITGAD):​c.2836A>C​(p.Lys946Gln) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ITGAD NM_005353.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.277
• Publications: 0 publications found

Genes affected

ITGAD (HGNC:6146): (integrin subunit alpha D) This gene belongs to the beta-2 integrin family of membrane glycoproteins, which are are composed of non-covalently linked alpha and beta subunits to form a heterodimer. It encodes the alpha subunit of the cell surface heterodimers and is involved in the activation and adhesion functions of leukocytes. The gene is located about 11kb downstream of the integrin subunit alpha X gene, another member of the integrin family. It is expressed in the tissue and circulating myeloid leukocytes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17936057).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005353.3. 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
	ITGAD	NM_005353.3	MANE Select	c.2836A>C	p.Lys946Gln	missense	Exon 24 of 30	NP_005344.2
	ITGAD	NM_001318185.2		c.2839A>C	p.Lys947Gln	missense	Exon 24 of 30	NP_001305114.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGAD	ENST00000389202.3	TSL:1 MANE Select	c.2836A>C	p.Lys946Gln	missense	Exon 24 of 30	ENSP00000373854.2	Q13349

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	1.7
DANN	Benign	0.88
DEOGEN2	Benign	0.055	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		-0.28
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.029
Sift	Benign	0.21	T
Sift4G	Benign	0.19	T
Polyphen		0.037	B
Vest4		0.24
MutPred		0.45		Loss of ubiquitination at K946 (P = 0.0098)
MVP		0.51
MPC		0.23
ClinPred		0.048	T
GERP RS		1.7
Varity_R		0.066
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

dbSNP: rs193921125; hg19: chr16-31434490; COSMIC: COSV54932900; COSMIC: COSV54932900;