1-21814782-C-T

Variant names:

• chr1-21814782-C-T
• rs372623125
• NM_001013693.3:c.470C>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001013693.3(LDLRAD2):​c.470C>T​(p.Pro157Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. P157H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LDLRAD2 NM_001013693.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.46
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.749

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013693.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LDLRAD2	NM_001013693.3	MANE Select	c.470C>T	p.Pro157Leu	missense	Exon 2 of 5	NP_001013715.2	Q5SZI1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LDLRAD2	ENST00000344642.7	TSL:2 MANE Select	c.470C>T	p.Pro157Leu	missense	Exon 2 of 5	ENSP00000340988.2	Q5SZI1
	LDLRAD2	ENST00000543870.1	TSL:1	c.470C>T	p.Pro157Leu	missense	Exon 2 of 6	ENSP00000444097.1	Q5SZI1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000110 AC: 1 AN: 91082 AF XY: 0.0000201

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000245

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1327070 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 649360

African (AFR) AF: 0.00 AC: 0 AN: 28508

American (AMR) AF: 0.00 AC: 0 AN: 22232

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19762

East Asian (EAS) AF: 0.00 AC: 0 AN: 35434

South Asian (SAS) AF: 0.00 AC: 0 AN: 67302

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40518

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5274

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1053178

Other (OTH) AF: 0.00 AC: 0 AN: 54862

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.054	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-0.66	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		6.5
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.35
Sift	Benign	0.030	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.69
MutPred		0.37		Gain of MoRF binding (P = 0.0494)
MVP		0.60
MPC		1.1
ClinPred		0.97	D
GERP RS		4.7
Varity_R		0.22
gMVP		0.52
Mutation Taster		=53/47	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs372623125; hg19: chr1-22141275;