rs721005

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr16-84872492-C-A
• chr16-84872492-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_031476.4(CRISPLD2):​c.965C>A​(p.Thr322Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CRISPLD2 NM_031476.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.45
• Publications: 0 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.846

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>A	p.Thr322Asn	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>A	p.Thr322Asn	missense	Exon 9 of 15	ENSP00000262424.5
	CRISPLD2	ENST00000564567.5	TSL:1	c.965C>A	p.Thr322Asn	missense	Exon 9 of 13	ENSP00000457655.1
	CRISPLD2	ENST00000567845.5	TSL:5	c.962C>A	p.Thr321Asn	missense	Exon 9 of 15	ENSP00000457183.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461324 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 726976

African (AFR) AF: 0.00 AC: 0 AN: 33446

American (AMR) AF: 0.00 AC: 0 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39654

South Asian (SAS) AF: 0.00 AC: 0 AN: 86176

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111656

Other (OTH) AF: 0.00 AC: 0 AN: 60380

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.090	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.33	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.088
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.85	T
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Uncertain	0.73	D
MutationAssessor	Uncertain	2.3	M
PhyloP100		5.5
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.48
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.58
MutPred		0.65		Gain of sheet (P = 0.0827)
MVP		0.81
MPC		0.33
ClinPred		0.93	D
GERP RS		5.0
Varity_R		0.60
gMVP		0.67

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

Other links and lift over

dbSNP: rs721005; hg19: chr16-84906098;