16-84838598-C-T

Position:

• chr16-84838598-C-T

Variant summary

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

The NM_031476.4(CRISPLD2):​c.103C>T​(p.Leu35Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 3.79

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRISPLD2	NM_031476.4	c.103C>T	p.Leu35Phe	missense_variant	2/15	ENST00000262424.10	NP_113664.1
CRISPLD2	XM_005256190.2	c.103C>T	p.Leu35Phe	missense_variant	3/16		XP_005256247.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRISPLD2	ENST00000262424.10	c.103C>T	p.Leu35Phe	missense_variant	2/15	1	NM_031476.4	ENSP00000262424	P4
	ENST00000648152.1	n.856+6470G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251466 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135908

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 06, 2023

The c.103C>T (p.L35F) alteration is located in exon 2 (coding exon 1) of the CRISPLD2 gene. This alteration results from a C to T substitution at nucleotide position 103, causing the leucine (L) at amino acid position 35 to be replaced by a phenylalanine (F). 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	0.19
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.028	T;T;.;.
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.94	D;D;D;D
M_CAP	Uncertain	0.085	D
MetaRNN	Uncertain	0.67	D;D;D;D
MetaSVM	Uncertain	0.051	D
MutationAssessor	Pathogenic	3.1	M;.;M;M
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-2.8	D;D;D;D
REVEL	Benign	0.26
Sift	Benign	0.033	D;D;D;D
Sift4G	Uncertain	0.014	D;D;D;D
Polyphen		0.63	P;.;D;D
Vest4		0.52
MutPred		0.34		Loss of loop (P = 0.0203);Loss of loop (P = 0.0203);Loss of loop (P = 0.0203);Loss of loop (P = 0.0203);
MVP		0.69
MPC		0.31
ClinPred		0.98	D
GERP RS		5.1
Varity_R		0.39
gMVP		0.69

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

LitVar

Other links and lift over

dbSNP: rs1473008847; hg19: chr16-84872204;