16-84838715-G-T

Position:

• chr16-84838715-G-T

Variant summary

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

The NM_031476.4(CRISPLD2):​c.220G>T​(p.Ala74Ser) 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: 4.59

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]

ENSG00000285848 (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.220G>T	p.Ala74Ser	missense_variant	2/15	ENST00000262424.10	NP_113664.1
CRISPLD2	XM_005256190.2	c.220G>T	p.Ala74Ser	missense_variant	3/16		XP_005256247.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRISPLD2	ENST00000262424.10	c.220G>T	p.Ala74Ser	missense_variant	2/15	1	NM_031476.4	ENSP00000262424.5

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 04, 2024

The c.220G>T (p.A74S) alteration is located in exon 2 (coding exon 1) of the CRISPLD2 gene. This alteration results from a G to T substitution at nucleotide position 220, causing the alanine (A) at amino acid position 74 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	0.18
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;T;.;.
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D;D;D;D
M_CAP	Benign	0.049	D
MetaRNN	Uncertain	0.54	D;D;D;D
MetaSVM	Benign	-0.43	T
MutationAssessor	Pathogenic	3.1	M;.;M;M
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-2.5	N;N;D;D
REVEL	Benign	0.29
Sift	Benign	0.031	D;D;D;D
Sift4G	Uncertain	0.0050	D;D;D;D
Polyphen		0.18	B;.;P;P
Vest4		0.33
MutPred		0.76		Gain of disorder (P = 0.0312);Gain of disorder (P = 0.0312);Gain of disorder (P = 0.0312);Gain of disorder (P = 0.0312);
MVP		0.47
MPC		0.17
ClinPred		0.98	D
GERP RS		5.3
Varity_R		0.30
gMVP		0.81

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: rs1376119814; hg19: chr16-84872321;