20-63873800-G-A

Position:

• chr20-63873800-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_003288.4(TPD52L2):​c.298G>A​(p.Val100Met) variant causes a missense change. The variant allele was found at a frequency of 0.00209 in 1,569,784 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0016 (2 hom., cov: 31)
  • Exomes 𝑓: 0.0021 (58 hom.)
• Consequence: TPD52L2 NM_003288.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.17

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005977899).
• BP6: Variant 20-63873800-G-A is Benign according to our data. Variant chr20-63873800-G-A is described in ClinVar as [Benign]. Clinvar id is 790891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00156 (237/152232) while in subpopulation SAS AF= 0.028 (135/4818). AF 95% confidence interval is 0.0242. There are 2 homozygotes in gnomad4. There are 150 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPD52L2	NM_003288.4	c.298G>A	p.Val100Met	missense_variant	3/7	ENST00000346249.9	NP_003279.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPD52L2	ENST00000346249.9	c.298G>A	p.Val100Met	missense_variant	3/7	1	NM_003288.4	ENSP00000343547

Frequencies

GnomAD3 genomes AF: 0.00156 AC: 237 AN: 152114 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0280

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000882

Gnomad OTH AF: 0.00288

GnomAD3 exomes AF: 0.00390 AC: 751 AN: 192472 Hom.: 12 AF XY: 0.00526 AC XY: 553 AN XY: 105052

Gnomad AFR exome AF: 0.0000833

Gnomad AMR exome AF: 0.00117

Gnomad ASJ exome AF: 0.00121

Gnomad EAS exome AF: 0.000380

Gnomad SAS exome AF: 0.0255

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000973

Gnomad OTH exome AF: 0.00324

GnomAD4 exome AF: 0.00214 AC: 3037 AN: 1417552 Hom.: 58 Cov.: 31 AF XY: 0.00292 AC XY: 2055 AN XY: 703414

Gnomad4 AFR exome AF: 0.000225

Gnomad4 AMR exome AF: 0.00108

Gnomad4 ASJ exome AF: 0.000727

Gnomad4 EAS exome AF: 0.000135

Gnomad4 SAS exome AF: 0.0269

Gnomad4 FIN exome AF: 0.0000384

Gnomad4 NFE exome AF: 0.000605

Gnomad4 OTH exome AF: 0.00213

GnomAD4 genome AF: 0.00156 AC: 237 AN: 152232 Hom.: 2 Cov.: 31 AF XY: 0.00202 AC XY: 150 AN XY: 74426

Gnomad4 AFR AF: 0.000168

Gnomad4 AMR AF: 0.00177

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0280

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000882

Gnomad4 OTH AF: 0.00285

Alfa AF: 0.000930 Hom.: 1

Bravo AF: 0.000850

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00105 AC: 9

ExAC AF: 0.00406 AC: 492

Asia WGS AF: 0.00693 AC: 26 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.097	T;T;.;T;.;.;.;.;.
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.42
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.88	D;D;D;D;D;D;D;D;D
MetaRNN	Benign	0.0060	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	.;.;.;L;L;L;L;L;L
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-2.1	.;.;N;N;D;N;N;N;N
REVEL	Benign	0.16
Sift	Benign	0.12	.;.;T;T;T;T;T;T;T
Sift4G	Benign	0.12	T;D;T;T;T;T;T;T;T
Polyphen		0.54, 0.28, 0.11	.;.;.;P;.;.;B;.;B
Vest4		0.33
MVP		0.11
MPC		0.19
ClinPred		0.028	T
GERP RS		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.050
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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

Other links and lift over

dbSNP: rs146221163; hg19: chr20-62505153; COSMIC: COSV53863721;