rs721005

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_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

Scores

1
9
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.45

Publications

0 publications found
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CRISPLD2NM_031476.4 linkc.965C>A p.Thr322Asn missense_variant Exon 9 of 15 ENST00000262424.10 NP_113664.1 Q9H0B8-1A0A140VK80
CRISPLD2XM_005256190.2 linkc.965C>A p.Thr322Asn missense_variant Exon 10 of 16 XP_005256247.1 Q9H0B8-1A0A140VK80

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CRISPLD2ENST00000262424.10 linkc.965C>A p.Thr322Asn missense_variant Exon 9 of 15 1 NM_031476.4 ENSP00000262424.5 Q9H0B8-1

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
show subpopulations
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
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T;.;D
Eigen
Benign
0.12
Eigen_PC
Benign
0.088
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.85
T;T;T;T
M_CAP
Uncertain
0.10
D
MetaRNN
Pathogenic
0.85
D;D;D;D
MetaSVM
Uncertain
0.73
D
MutationAssessor
Uncertain
2.3
M;.;M;.
PhyloP100
5.5
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-2.2
N;N;N;N
REVEL
Uncertain
0.48
Sift
Uncertain
0.0020
D;D;D;D
Sift4G
Uncertain
0.0030
D;D;D;D
Polyphen
1.0
D;.;B;.
Vest4
0.58
MutPred
0.65
Gain of sheet (P = 0.0827);.;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

Publications

Other links and lift over

dbSNP: rs721005; hg19: chr16-84906098; API