Variant chr1-21814790-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001013693.3(LDLRAD2):c.478G>T(p.Asp160Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000755 in 1,324,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. D160H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.6e-7 ( 0 hom. )

Consequence

LDLRAD2
NM_001013693.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.27

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.8

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LDLRAD2	NM_001013693.3 link	c.478G>T	p.Asp160Tyr	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.478G>T	p.Asp160Tyr	missense_variant	Exon 2 of 5	2	NM_001013693.3	ENSP00000340988.2		Q5SZI1
LDLRAD2	ENST00000543870.1 link	c.478G>T	p.Asp160Tyr	missense_variant	Exon 2 of 6	1		ENSP00000444097.1		Q5SZI1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.55e-7

AC:

AN:

1324160

Hom.:

Cov.:

AF XY:

0.00000154

AC XY:

AN XY:

647380

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000444

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.90

BayesDel_addAF

Uncertain

0.032

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

T;T

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.84

.;T

M_CAP

Uncertain

0.11

MetaRNN

Pathogenic

0.80

D;D

MetaSVM

Benign

-0.83

MutationAssessor

Uncertain

2.2

M;M

PrimateAI

Uncertain

0.65

PROVEAN

Pathogenic

-4.7

D;D

REVEL

Uncertain

0.30

Sift

Uncertain

0.020

D;D

Sift4G

Uncertain

0.010

D;D

Polyphen

1.0

D;D

Vest4

0.81

MutPred

0.54

Gain of MoRF binding (P = 0.0615);Gain of MoRF binding (P = 0.0615);

MVP

0.62

MPC

1.2

ClinPred

0.98

GERP RS

3.8

Varity_R

0.21

gMVP

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over