16-84872492-C-G

Variant names:

• chr16-84872492-C-G
• rs721005
• NM_031476.4:c.965C>G

Variant summary

Our verdict is Benign. The variant received -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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 36 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031476.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRISPLD2	NM_031476.4	MANE Select	c.965C>G	p.Thr322Ser	missense	Exon 9 of 15	NP_113664.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRISPLD2	ENST00000262424.10	TSL:1 MANE Select	c.965C>G	p.Thr322Ser	missense	Exon 9 of 15	ENSP00000262424.5
	CRISPLD2	ENST00000564567.5	TSL:1	c.965C>G	p.Thr322Ser	missense	Exon 9 of 13	ENSP00000457655.1
	CRISPLD2	ENST00000567845.5	TSL:5	c.962C>G	p.Thr321Ser	missense	Exon 9 of 15	ENSP00000457183.1

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

GnomAD2 exomes AF: 0.399 AC: 100087 AN: 250710 AF XY: 0.401

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 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

African (AFR) AF: 0.541 AC: 18052 AN: 33368

American (AMR) AF: 0.284 AC: 12681 AN: 44602

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 9638 AN: 26108

East Asian (EAS) AF: 0.614 AC: 24320 AN: 39612

South Asian (SAS) AF: 0.429 AC: 36888 AN: 86048

European-Finnish (FIN) AF: 0.328 AC: 17528 AN: 53408

Middle Eastern (MID) AF: 0.392 AC: 2260 AN: 5762

European-Non Finnish (NFE) AF: 0.385 AC: 427423 AN: 1109810

Other (OTH) AF: 0.408 AC: 24608 AN: 60310

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

African (AFR) AF: 0.537 AC: 22265 AN: 41466

American (AMR) AF: 0.357 AC: 5454 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1299 AN: 3470

East Asian (EAS) AF: 0.659 AC: 3409 AN: 5172

South Asian (SAS) AF: 0.448 AC: 2158 AN: 4822

European-Finnish (FIN) AF: 0.333 AC: 3521 AN: 10568

Middle Eastern (MID) AF: 0.455 AC: 132 AN: 290

European-Non Finnish (NFE) AF: 0.380 AC: 25837 AN: 67976

Other (OTH) AF: 0.445 AC: 939 AN: 2112

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 v4.9

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
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.56	T
MetaRNN	Benign	0.000011	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.4	L
PhyloP100		5.5
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.40
Sift	Benign	0.63	T
Sift4G	Benign	0.41	T
Polyphen		0.46	P
Vest4		0.091
MutPred		0.28		Gain of sheet (P = 0.0827)
MPC		0.11
ClinPred		0.044	T
GERP RS		5.0
Varity_R		0.18
gMVP		0.45
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		1.0
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

Other links and lift over

dbSNP: rs721005; hg19: chr16-84906098; COSMIC: COSV52277833;