Variant 16-31397454-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.233C>T(p.Pro78Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000069 in 1,594,030 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00028 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

ITGAD
ENST00000389202.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.01

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:

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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=0.026181191).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGAD	NM_005353.3 linkuse as main transcript	c.233C>T	p.Pro78Leu	missense_variant	3/30	ENST00000389202.3	NP_005344.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGAD	ENST00000389202.3 linkuse as main transcript	c.233C>T	p.Pro78Leu	missense_variant	3/30	1	NM_005353.3	ENSP00000373854	P1
ITGAD	ENST00000444228.2 linkuse as main transcript	n.259C>T		non_coding_transcript_exon_variant	3/9	2

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000135

AC:

AN:

214246

Hom.:

AF XY:

0.000164

AC XY:

AN XY:

115698

show subpopulations

Gnomad AFR exome

AF:

0.000459

Gnomad AMR exome

AF:

0.0000328

Gnomad ASJ exome

AF:

0.00141

Gnomad EAS exome

AF:

0.000250

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000316

Gnomad OTH exome

AF:

0.000374

GnomAD4 exome

AF:

0.0000472

AC:

AN:

1441822

Hom.:

Cov.:

AF XY:

0.0000517

AC XY:

AN XY:

715334

show subpopulations

Gnomad4 AFR exome

AF:

0.000422

Gnomad4 AMR exome

AF:

0.0000479

Gnomad4 ASJ exome

AF:

0.00117

Gnomad4 EAS exome

AF:

0.000310

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000363

Gnomad4 OTH exome

AF:

0.000101

GnomAD4 genome

AF:

0.000276

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.000796

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.000577

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000180

Hom.:

Bravo

AF:

0.000280

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000116

AC:

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

May 09, 2024

The c.233C>T (p.P78L) alteration is located in exon 3 (coding exon 3) of the ITGAD gene. This alteration results from a C to T substitution at nucleotide position 233, causing the proline (P) at amino acid position 78 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

0.076

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.60

CADD

Benign

0.36

DANN

Benign

0.50

DEOGEN2

Uncertain

0.42

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0062

LIST_S2

Benign

0.23

M_CAP

Benign

0.014

MetaRNN

Benign

0.026

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.39

MutationTaster

Benign

1.0

PrimateAI

Benign

0.24

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.082

Sift

Benign

0.56

Sift4G

Benign

0.41

Polyphen

0.012

Vest4

0.10

MVP

0.50

MPC

0.19

ClinPred

0.0054

GERP RS

-1.6

Varity_R

0.035

gMVP

0.25

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