Variant 9-35612921-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001782.3(CD72):c.761G>T(p.Trp254Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000057 in 1,613,848 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 2 hom., cov: 32)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

CD72
NM_001782.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.65

Variant links:

Genes affected

CD72 (HGNC:1696): (CD72 molecule) Predicted to enable signaling receptor binding activity. Predicted to be involved in cell adhesion. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CD72 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.32247683).

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD72	NM_001782.3 linkuse as main transcript	c.761G>T	p.Trp254Leu	missense_variant	6/9	ENST00000259633.9	NP_001773.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD72	ENST00000259633.9 linkuse as main transcript	c.761G>T	p.Trp254Leu	missense_variant	6/9	1	NM_001782.3	ENSP00000259633	P1
CD72	ENST00000490239.5 linkuse as main transcript	n.1142G>T		non_coding_transcript_exon_variant	5/8	1

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00236

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000111

AC:

AN:

251418

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000781

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000356

AC:

AN:

1461694

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.000962

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.000263

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.000417

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.0000966

Gnomad4 AMR

AF:

0.00236

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000564

Hom.:

Bravo

AF:

0.000366

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000247

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

Oct 30, 2023

The c.761G>T (p.W254L) alteration is located in exon 6 (coding exon 6) of the CD72 gene. This alteration results from a G to T substitution at nucleotide position 761, causing the tryptophan (W) at amino acid position 254 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

Pathogenic

0.63

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Uncertain

0.52

D;D;.

Eigen

Benign

-0.069

Eigen_PC

Benign

-0.093

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.47

.;T;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.32

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.6

L;L;.

MutationTaster

Benign

0.74

D;D

PrimateAI

Benign

0.43

PROVEAN

Pathogenic

-10

D;D;.

REVEL

Benign

0.26

Sift

Benign

0.34

T;T;.

Sift4G

Benign

0.38

T;T;T

Polyphen

0.69

P;P;.

Vest4

0.47

MVP

0.36

MPC

1.0

ClinPred

0.25

GERP RS

4.6

Varity_R

0.31

gMVP

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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