Variant chr16-31407830-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000389202.3(ITGAD):c.923C>T(p.Pro308Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000738 in 1,612,280 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000069 ( 1 hom. )

Consequence

ITGAD
ENST00000389202.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0440

Variant links:

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]

ITGAD links:

ITGAD (HGNC:):

ITGAD links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0661872).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGAD	NM_005353.3 linkuse as main transcript	c.923C>T	p.Pro308Leu	missense_variant	9/30	ENST00000389202.3	NP_005344.2	Q13349Q59H14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGAD	ENST00000389202.3 linkuse as main transcript	c.923C>T	p.Pro308Leu	missense_variant	9/30	1	NM_005353.3	ENSP00000373854.2		Q13349
ITGAD	ENST00000444228.2 linkuse as main transcript	n.1046C>T		non_coding_transcript_exon_variant	8/9	2

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000123

AC:

AN:

251214

Hom.:

AF XY:

0.0000883

AC XY:

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.000555

Gnomad AMR exome

AF:

0.000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000616

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.0000692

AC:

101

AN:

1460124

Hom.:

Cov.:

AF XY:

0.0000620

AC XY:

AN XY:

725928

show subpopulations

Gnomad4 AFR exome

AF:

0.000419

Gnomad4 AMR exome

AF:

0.000268

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:

0.0000558

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.000118

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.000314

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000966

Hom.:

Bravo

AF:

0.000219

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000683

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000906

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 25, 2022

The c.923C>T (p.P308L) alteration is located in exon 9 (coding exon 9) of the ITGAD gene. This alteration results from a C to T substitution at nucleotide position 923, causing the proline (P) at amino acid position 308 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

0.088

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Uncertain

0.46

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.75

M_CAP

Benign

0.011

MetaRNN

Benign

0.066

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.76

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

-2.0

REVEL

Benign

0.042

Sift

Uncertain

0.016

Sift4G

Uncertain

0.039

Polyphen

0.10

Vest4

0.19

MVP

0.49

MPC

0.19

ClinPred

0.016

GERP RS

2.7

Varity_R

0.056

gMVP

0.39

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over