16-84845894-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_031476.4(CRISPLD2):c.349C>T(p.His117Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CRISPLD2 NM_031476.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.45

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.837

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRISPLD2	NM_031476.4	c.349C>T	p.His117Tyr	missense_variant	3/15	ENST00000262424.10
CRISPLD2	XM_005256190.2	c.349C>T	p.His117Tyr	missense_variant	4/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRISPLD2	ENST00000262424.10	c.349C>T	p.His117Tyr	missense_variant	3/15	1	NM_031476.4	P4
	ENST00000648152.1	n.550G>A		non_coding_transcript_exon_variant	3/6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

May 18, 2023

The c.349C>T (p.H117Y) alteration is located in exon 3 (coding exon 2) of the CRISPLD2 gene. This alteration results from a C to T substitution at nucleotide position 349, causing the histidine (H) at amino acid position 117 to be replaced by a tyrosine (Y). 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	Pathogenic	0.57
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
Cadd	Uncertain	26
Dann	Uncertain	1.0
DEOGEN2	Benign	0.036	T;T;.;.
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.88	D;D;D;T
M_CAP	Benign	0.034	D
MetaRNN	Pathogenic	0.84	D;D;D;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	0.98	L;.;L;L
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-4.7	D;D;D;D
REVEL	Uncertain	0.30
Sift	Benign	0.11	T;T;T;D
Sift4G	Uncertain	0.058	T;T;T;D
Polyphen		1.0	D;.;B;D
Vest4		0.91
MutPred		0.68		Gain of catalytic residue at H117 (P = 0.0415);Gain of catalytic residue at H117 (P = 0.0415);Gain of catalytic residue at H117 (P = 0.0415);Gain of catalytic residue at H117 (P = 0.0415);
MVP		0.40
MPC		0.36
ClinPred		1.0	D
GERP RS		5.2
Varity_R		0.55
gMVP		0.89

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: chr16-84879500;