1-21814637-C-T

Variant names:

• chr1-21814637-C-T
• NM_001013693.3:c.325C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001013693.3(LDLRAD2):​c.325C>T​(p.Pro109Ser) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LDLRAD2 NM_001013693.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.496

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.036147535).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LDLRAD2	NM_001013693.3	c.325C>T	p.Pro109Ser	missense_variant	Exon 2 of 5	ENST00000344642.7	NP_001013715.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LDLRAD2	ENST00000344642.7	c.325C>T	p.Pro109Ser	missense_variant	Exon 2 of 5	2	NM_001013693.3	ENSP00000340988.2
LDLRAD2	ENST00000543870.1	c.325C>T	p.Pro109Ser	missense_variant	Exon 2 of 6	1		ENSP00000444097.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 20, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.325C>T (p.P109S) alteration is located in exon 2 (coding exon 2) of the LDLRAD2 gene. This alteration results from a C to T substitution at nucleotide position 325, causing the proline (P) at amino acid position 109 to be replaced by a serine (S). 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	Benign	0.098
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	7.7
DANN	Benign	0.94
DEOGEN2	Benign	0.018	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.68	.;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.036	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.88	N;N
REVEL	Benign	0.024
Sift	Benign	0.56	T;T
Sift4G	Benign	0.31	T;T
Polyphen		0.046	B;B
Vest4		0.061
MutPred		0.27		Gain of glycosylation at P109 (P = 0.0376);Gain of glycosylation at P109 (P = 0.0376);
MVP		0.19
MPC		0.44
ClinPred		0.060	T
GERP RS		-0.19
Varity_R		0.033
gMVP		0.19

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-22141130;