16-84849395-C-G

Position:

• chr16-84849395-C-G

Variant summary

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

The NM_031476.4(CRISPLD2):​c.370C>G​(p.Pro124Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P124P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CRISPLD2 NM_031476.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.95

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	UniProt
CRISPLD2	NM_031476.4	c.370C>G	p.Pro124Ala	missense_variant	4/15	ENST00000262424.10
CRISPLD2	XM_005256190.2	c.370C>G	p.Pro124Ala	missense_variant	5/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRISPLD2	ENST00000262424.10	c.370C>G	p.Pro124Ala	missense_variant	4/15	1	NM_031476.4	P4
	ENST00000648152.1	n.373-561G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 42

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

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

Feb 06, 2024

The c.370C>G (p.P124A) alteration is located in exon 4 (coding exon 3) of the CRISPLD2 gene. This alteration results from a C to G substitution at nucleotide position 370, causing the proline (P) at amino acid position 124 to be replaced by an alanine (A). 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	Uncertain	0.41
BayesDel_addAF	Benign	-0.010	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	23
DANN	Benign	0.91
DEOGEN2	Benign	0.035	T;T;.
Eigen	Benign	0.079
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.81	T;T;T
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.62	D;D;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	0.94	L;.;L
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-3.6	D;D;D
REVEL	Uncertain	0.30
Sift	Benign	0.081	T;T;T
Sift4G	Uncertain	0.046	D;D;T
Polyphen		0.0090	B;.;B
Vest4		0.74
MutPred		0.61		Gain of MoRF binding (P = 0.0358);Gain of MoRF binding (P = 0.0358);Gain of MoRF binding (P = 0.0358);
MVP		0.27
MPC		0.34
ClinPred		0.92	D
GERP RS		5.7
Varity_R		0.26
gMVP		0.80

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: rs1293006248; hg19: chr16-84883001;