Variant 1-21814719-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001013693.3(LDLRAD2):c.407C>G(p.Pro136Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000854 in 1,404,960 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000085 ( 0 hom. )

Consequence

LDLRAD2
NM_001013693.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.80

Variant links:

Genes affected

LDLRAD2 (HGNC:32071): (low density lipoprotein receptor class A domain containing 2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LDLRAD2 links:

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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
LDLRAD2	NM_001013693.3 link	c.407C>G	p.Pro136Arg	missense_variant	Exon 2 of 5	ENST00000344642.7	NP_001013715.2	Q5SZI1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LDLRAD2	ENST00000344642.7 link	c.407C>G	p.Pro136Arg	missense_variant	Exon 2 of 5	2	NM_001013693.3	ENSP00000340988.2		Q5SZI1
LDLRAD2	ENST00000543870.1 link	c.407C>G	p.Pro136Arg	missense_variant	Exon 2 of 6	1		ENSP00000444097.1		Q5SZI1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000658

AC:

AN:

152018

Hom.:

AF XY:

0.0000120

AC XY:

AN XY:

83490

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000899

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:

0.00000854

AC:

AN:

1404960

Hom.:

Cov.:

AF XY:

0.00000720

AC XY:

AN XY:

694710

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000553

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000172

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000189

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 18, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.407C>G (p.P136R) alteration is located in exon 2 (coding exon 2) of the LDLRAD2 gene. This alteration results from a C to G substitution at nucleotide position 407, causing the proline (P) at amino acid position 136 to be replaced by an arginine (R). 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

-0.14

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

T;T

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.53

.;T

M_CAP

Uncertain

0.088

MetaRNN

Uncertain

0.58

D;D

MetaSVM

Benign

-0.39

MutationAssessor

Uncertain

2.3

M;M

PrimateAI

Uncertain

0.79

PROVEAN

Pathogenic

-5.5

D;D

REVEL

Benign

0.26

Sift

Uncertain

0.019

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.52

MutPred

0.30

Gain of catalytic residue at S141 (P = 0.0761);Gain of catalytic residue at S141 (P = 0.0761);

MVP

0.64

MPC

1.1

ClinPred

0.98

GERP RS

4.8

Varity_R

0.41

gMVP

0.57

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

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