rs1024032389

Variant names:

• chr1-21814670-C-G
• rs1024032389
• NM_001013693.3:c.358C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-21814670-C-G
• chr1-21814670-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001013693.3(LDLRAD2):​c.358C>G​(p.Pro120Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000699 in 1,430,266 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. P120S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: LDLRAD2 NM_001013693.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10
• 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: 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=0.04838282).

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.358C>G	p.Pro120Ala	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.358C>G	p.Pro120Ala	missense	Exon 2 of 5	ENSP00000340988.2	Q5SZI1
	LDLRAD2	ENST00000543870.1	TSL:1	c.358C>G	p.Pro120Ala	missense	Exon 2 of 6	ENSP00000444097.1	Q5SZI1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.99e-7 AC: 1 AN: 1430266 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 709492

African (AFR) AF: 0.00 AC: 0 AN: 32326

American (AMR) AF: 0.00 AC: 0 AN: 39700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25540

East Asian (EAS) AF: 0.00 AC: 0 AN: 37564

South Asian (SAS) AF: 0.0000120 AC: 1 AN: 83544

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49548

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5474

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1097484

Other (OTH) AF: 0.00 AC: 0 AN: 59086

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	12
DANN	Benign	0.84
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.073	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	M
PhyloP100		1.1
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.061
Sift	Benign	0.72	T
Sift4G	Benign	0.26	T
Polyphen		0.063	B
Vest4		0.15
MutPred		0.13		Loss of glycosylation at P120 (P = 0.0101)
MVP		0.23
MPC		0.33
ClinPred		0.044	T
GERP RS		0.29
Varity_R		0.026
gMVP		0.20
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs1024032389; hg19: chr1-22141163;