5-178153827-C-A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_017838.4(NHP2):​c.-10G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000208 in 1,602,630 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00019 ( 1 hom. )

Consequence

NHP2
NM_017838.4 5_prime_UTR_premature_start_codon_gain

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.14

Publications

0 publications found
Variant links:
Genes affected
NHP2 (HGNC:14377): (NHP2 ribonucleoprotein) This gene is a member of the H/ACA snoRNPs (small nucleolar ribonucleoproteins) gene family. snoRNPs are involved in various aspects of rRNA processing and modification and have been classified into two families: C/D and H/ACA. The H/ACA snoRNPs also include the DKC1, NOLA1 and NOLA3 proteins. These four H/ACA snoRNP proteins localize to the dense fibrillar components of nucleoli and to coiled (Cajal) bodies in the nucleus. Both 18S rRNA production and rRNA pseudouridylation are impaired if any one of the four proteins is depleted. The four H/ACA snoRNP proteins are also components of the telomerase complex. This gene encodes a protein related to Saccharomyces cerevisiae Nhp2p. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2008]
NHP2 Gene-Disease associations (from GenCC):
  • dyskeratosis congenita, autosomal recessive 2
    Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
  • dyskeratosis congenita
    Inheritance: AD, AR Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, ClinGen

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BP6
Variant 5-178153827-C-A is Benign according to our data. Variant chr5-178153827-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 353029.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NHP2NM_017838.4 linkc.-10G>T 5_prime_UTR_premature_start_codon_gain_variant Exon 1 of 4 ENST00000274606.8 NP_060308.1 Q9NX24
NHP2NM_017838.4 linkc.-10G>T 5_prime_UTR_variant Exon 1 of 4 ENST00000274606.8 NP_060308.1 Q9NX24

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NHP2ENST00000274606.8 linkc.-10G>T 5_prime_UTR_premature_start_codon_gain_variant Exon 1 of 4 1 NM_017838.4 ENSP00000274606.4 Q9NX24
NHP2ENST00000274606.8 linkc.-10G>T 5_prime_UTR_variant Exon 1 of 4 1 NM_017838.4 ENSP00000274606.4 Q9NX24

Frequencies

GnomAD3 genomes
AF:
0.000309
AC:
47
AN:
152246
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000458
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000523
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000176
Gnomad OTH
AF:
0.00382
GnomAD2 exomes
AF:
0.000175
AC:
39
AN:
223090
AF XY:
0.000180
show subpopulations
Gnomad AFR exome
AF:
0.000456
Gnomad AMR exome
AF:
0.000348
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000222
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000194
AC:
282
AN:
1450266
Hom.:
1
Cov.:
31
AF XY:
0.000197
AC XY:
142
AN XY:
720840
show subpopulations
African (AFR)
AF:
0.000934
AC:
31
AN:
33192
American (AMR)
AF:
0.000422
AC:
18
AN:
42624
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25868
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39022
South Asian (SAS)
AF:
0.0000118
AC:
1
AN:
84940
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52106
Middle Eastern (MID)
AF:
0.00157
AC:
9
AN:
5750
European-Non Finnish (NFE)
AF:
0.000173
AC:
192
AN:
1106898
Other (OTH)
AF:
0.000518
AC:
31
AN:
59866
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.469
Heterozygous variant carriers
0
15
30
46
61
76
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
10
20
30
40
50
<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
AF:
0.000341
AC:
52
AN:
152364
Hom.:
0
Cov.:
33
AF XY:
0.000309
AC XY:
23
AN XY:
74514
show subpopulations
African (AFR)
AF:
0.000577
AC:
24
AN:
41590
American (AMR)
AF:
0.000523
AC:
8
AN:
15310
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5176
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4834
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10626
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.000176
AC:
12
AN:
68036
Other (OTH)
AF:
0.00378
AC:
8
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.491
Heterozygous variant carriers
0
3
6
10
13
16
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome 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
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.000438

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Dec 17, 2021
Genetic Services Laboratory, University of Chicago
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.71
CADD
Benign
2.6
DANN
Benign
0.64
PhyloP100
-2.1
PromoterAI
-0.082
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Mutation Taster
=300/0
polymorphism

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: rs371173524; hg19: chr5-177580828; API