16-84838653-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031476.4(CRISPLD2):c.158G>C(p.Arg53Thr) 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. 14/21 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: CRISPLD2 NM_031476.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.19

Genes affected

CRISPLD2 (HGNC:25248): (cysteine rich secretory protein LCCL domain containing 2) Predicted to enable glycosaminoglycan binding activity. Involved in face morphogenesis. Located in transport vesicle. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13803488).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRISPLD2	NM_031476.4	c.158G>C	p.Arg53Thr	missense_variant	2/15	ENST00000262424.10
CRISPLD2	XM_005256190.2	c.158G>C	p.Arg53Thr	missense_variant	3/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRISPLD2	ENST00000262424.10	c.158G>C	p.Arg53Thr	missense_variant	2/15	1	NM_031476.4	P4
	ENST00000648152.1	n.856+6415C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 12, 2023

The c.158G>C (p.R53T) alteration is located in exon 2 (coding exon 1) of the CRISPLD2 gene. This alteration results from a G to C substitution at nucleotide position 158, causing the arginine (R) at amino acid position 53 to be replaced by a threonine (T). 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	0.12
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
Cadd	Benign	11
Dann	Benign	0.73
DEOGEN2	Benign	0.0040	T;T;.;.
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.74	T;T;T;T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.14	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M;.;M;M
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.98	N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.56	T;T;T;T
Sift4G	Benign	0.54	T;T;T;T
Polyphen		0.0060	B;.;B;B
Vest4		0.25
MutPred		0.42		Loss of MoRF binding (P = 0.0196);Loss of MoRF binding (P = 0.0196);Loss of MoRF binding (P = 0.0196);Loss of MoRF binding (P = 0.0196);
MVP		0.49
MPC		0.081
ClinPred		0.057	T
GERP RS		-1.2
Varity_R		0.042
gMVP		0.46

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-84872259;