rs721005

Positions:

• chr16-84872492-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031476.4(CRISPLD2):​c.965C>G​(p.Thr322Ser) variant causes a missense change. The variant allele was found at a frequency of 0.396 in 1,611,090 control chromosomes in the GnomAD database, including 129,932 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.43 (14598 hom., cov: 32)
  • Exomes 𝑓: 0.39 (115334 hom.)
• Consequence: CRISPLD2 NM_031476.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.45

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]

CRISPLD2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.0684134E-5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRISPLD2	NM_031476.4	c.965C>G	p.Thr322Ser	missense_variant	9/15	ENST00000262424.10	NP_113664.1
CRISPLD2	XM_005256190.2	c.965C>G	p.Thr322Ser	missense_variant	10/16		XP_005256247.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRISPLD2	ENST00000262424.10	c.965C>G	p.Thr322Ser	missense_variant	9/15	1	NM_031476.4	ENSP00000262424.5

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65256 AN: 151946 Hom.: 14579 Cov.: 32

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.659

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.380

Gnomad OTH AF: 0.440

GnomAD3 exomes AF: 0.399 AC: 100087 AN: 250710 Hom.: 21390 AF XY: 0.401 AC XY: 54414 AN XY: 135542

Gnomad AFR exome AF: 0.539

Gnomad AMR exome AF: 0.275

Gnomad ASJ exome AF: 0.370

Gnomad EAS exome AF: 0.673

Gnomad SAS exome AF: 0.428

Gnomad FIN exome AF: 0.325

Gnomad NFE exome AF: 0.382

Gnomad OTH exome AF: 0.392

GnomAD4 exome AF: 0.393 AC: 573398 AN: 1459028 Hom.: 115334 Cov.: 34 AF XY: 0.394 AC XY: 285777 AN XY: 725910

Gnomad4 AFR exome AF: 0.541

Gnomad4 AMR exome AF: 0.284

Gnomad4 ASJ exome AF: 0.369

Gnomad4 EAS exome AF: 0.614

Gnomad4 SAS exome AF: 0.429

Gnomad4 FIN exome AF: 0.328

Gnomad4 NFE exome AF: 0.385

Gnomad4 OTH exome AF: 0.408

GnomAD4 genome AF: 0.430 AC: 65315 AN: 152062 Hom.: 14598 Cov.: 32 AF XY: 0.428 AC XY: 31831 AN XY: 74334

Gnomad4 AFR AF: 0.537

Gnomad4 AMR AF: 0.357

Gnomad4 ASJ AF: 0.374

Gnomad4 EAS AF: 0.659

Gnomad4 SAS AF: 0.448

Gnomad4 FIN AF: 0.333

Gnomad4 NFE AF: 0.380

Gnomad4 OTH AF: 0.445

Alfa AF: 0.394 Hom.: 9103

Bravo AF: 0.436

TwinsUK AF: 0.383 AC: 1421

ALSPAC AF: 0.374 AC: 1442

ESP6500AA AF: 0.546 AC: 2403

ESP6500EA AF: 0.388 AC: 3337

ExAC AF: 0.408 AC: 49536

Asia WGS AF: 0.512 AC: 1779 AN: 3478

EpiCase AF: 0.387

EpiControl AF: 0.385

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	18
DANN	Benign	0.56
DEOGEN2	Benign	0.23	T;T;.;T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.56	T;T;T;T
MetaRNN	Benign	0.000011	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.4	L;.;L;.
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.4	N;N;N;N
REVEL	Uncertain	0.40
Sift	Benign	0.63	T;T;T;T
Sift4G	Benign	0.41	T;T;T;T
Polyphen		0.46	P;.;B;.
Vest4		0.091
MutPred		0.28		Gain of sheet (P = 0.0827);.;Gain of sheet (P = 0.0827);.;
MPC		0.11
ClinPred		0.044	T
GERP RS		5.0
Varity_R		0.18
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs721005; hg19: chr16-84906098; COSMIC: COSV52277833;