Genetic Variant CD72:p.Gly291Cys (chr9-35611883-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001782.3(CD72):c.871G>T(p.Gly291Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CD72
NM_001782.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -4.18

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD72	NM_001782.3 link	c.871G>T	p.Gly291Cys	missense_variant	Exon 7 of 9	ENST00000259633.9	NP_001773.1	P21854Q5TLG3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD72	ENST00000259633.9 link	c.871G>T	p.Gly291Cys	missense_variant	Exon 7 of 9	1	NM_001782.3	ENSP00000259633.4		P21854
CD72	ENST00000490239.5 link	n.1252G>T		non_coding_transcript_exon_variant	Exon 6 of 8	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251208

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

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:

0.00000137

AC:

AN:

1458100

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725660

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.871G>T (p.G291C) alteration is located in exon 7 (coding exon 7) of the CD72 gene. This alteration results from a G to T substitution at nucleotide position 871, causing the glycine (G) at amino acid position 291 to be replaced by a cysteine (C). 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

Uncertain

0.37

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.0070

DANN

Benign

0.41

DEOGEN2

Benign

0.12

T;T;.

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.40

.;T;T

M_CAP

Benign

0.0025

MetaRNN

Benign

0.087

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;L;.

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.2

N;N;.

REVEL

Benign

0.040

Sift

Benign

0.13

T;T;.

Sift4G

Uncertain

0.048

D;D;D

Polyphen

0.0010

B;B;.

Vest4

0.23

MutPred

0.57

Loss of disorder (P = 0.0121);Loss of disorder (P = 0.0121);Loss of disorder (P = 0.0121);

MVP

0.16

MPC

0.60

ClinPred

0.049

GERP RS

-8.7

Varity_R

0.073

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.28

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.28

Position offset: -10

DS_AL_spliceai

0.20

Position offset: 36

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