20-63889224-G-C

Variant names:

• chr20-63889224-G-C
• NM_003288.4:c.511G>C

Variant summary

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

The NM_003288.4(TPD52L2):​c.511G>C​(p.Val171Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TPD52L2 NM_003288.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.43

Genes affected

TPD52L2 (HGNC:12007): (TPD52 like 2) This gene encodes a member of the tumor protein D52-like family. These proteins are characterized by an N-terminal coiled-coil motif that is used to form homo- and heteromeric complexes with other tumor protein D52-like proteins. Expression of this gene may be a marker for breast cancer and acute lymphoblastic leukemia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 12. [provided by RefSeq, Aug 2011]

ENSG00000290226 (HGNC:):

ACMG classification

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
TPD52L2	NM_003288.4	c.511G>C	p.Val171Leu	missense_variant	Exon 6 of 7	ENST00000346249.9	NP_003279.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPD52L2	ENST00000346249.9	c.511G>C	p.Val171Leu	missense_variant	Exon 6 of 7	1	NM_003288.4	ENSP00000343547.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.580G>C (p.V194L) alteration is located in exon 8 (coding exon 8) of the TPD52L2 gene. This alteration results from a G to C substitution at nucleotide position 580, causing the valine (V) at amino acid position 194 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	0.68
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.093	T;.;T;.;.;.;.;.
Eigen	Uncertain	0.68
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.87	D;T;D;T;D;T;T;D
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.58	D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.6	.;.;M;.;.;.;.;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.1	.;N;N;N;N;N;N;N
REVEL	Benign	0.24
Sift	Uncertain	0.0030	.;D;D;D;D;D;D;D
Sift4G	Benign	0.090	T;T;T;T;T;T;D;T
Polyphen		0.98, 1.0, 0.84	.;.;D;.;.;D;.;P
Vest4		0.35
MutPred		0.88		.;.;Loss of MoRF binding (P = 0.0975);.;.;.;.;.;
MVP		0.43
MPC		0.60
ClinPred		0.93	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.24
gMVP		0.50

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-62520577;