dbSNP rs750941637: TPD52L2:p.Ala33Gly (chr20-63869374-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003288.4(TPD52L2):c.98C>G(p.Ala33Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A33V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

TPD52L2
NM_003288.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.66

Publications

0 publications found

Variant links:

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]

TPD52L2 links:

ENSG00000290226 (HGNC:):

ENSG00000290226 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03622386).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003288.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TPD52L2	NM_003288.4	MANE Select	c.98C>G	p.Ala33Gly	missense	Exon 2 of 7	NP_003279.2
TPD52L2	NM_199360.3		c.98C>G	p.Ala33Gly	missense	Exon 2 of 9	NP_955392.1	O43399-7
TPD52L2	NM_001243895.2		c.98C>G	p.Ala33Gly	missense	Exon 2 of 6	NP_001230824.1	A0A087WYR3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TPD52L2	ENST00000346249.9	TSL:1 MANE Select	c.98C>G	p.Ala33Gly	missense	Exon 2 of 7	ENSP00000343547.4	O43399-1
TPD52L2	ENST00000352482.8	TSL:1	c.98C>G	p.Ala33Gly	missense	Exon 2 of 8	ENSP00000344647.4	O43399-5
TPD52L2	ENST00000348257.9	TSL:1	c.98C>G	p.Ala33Gly	missense	Exon 2 of 6	ENSP00000343554.5	O43399-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000398

AC:

AN:

251312

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.000557

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.000329

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.032

Eigen

Benign

-0.079

Eigen_PC

Benign

0.043

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.83

M_CAP

Benign

0.0060

MetaRNN

Benign

0.036

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.8

PhyloP100

1.7

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.8

REVEL

Benign

0.11

Sift

Benign

0.14

Sift4G

Benign

0.13

Polyphen

0.0

Vest4

0.11

MutPred

0.50

Gain of relative solvent accessibility (P = 0.0082)

MVP

0.14

MPC

0.15

ClinPred

0.044

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.087

gMVP

0.14

Mutation Taster

=63/37

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over