rs371173524

Variant names:

Your query was ambiguous. Multiple possible variants found:

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

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

NHP2 links:

ENSG00000289726 (HGNC:):

ENSG00000289726 links:

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 CliVar as Likely_benign. Clinvar id is 353029.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-178153827-C-A is described in CliVar as Likely_benign. Clinvar id is 353029.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-178153827-C-A is described in CliVar as Likely_benign. Clinvar id is 353029.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-178153827-C-A is described in CliVar as Likely_benign. Clinvar id is 353029.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-178153827-C-A is described in CliVar as Likely_benign. Clinvar id is 353029.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-178153827-C-A is described in CliVar as Likely_benign. Clinvar id is 353029.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-178153827-C-A is described in CliVar as Likely_benign. Clinvar id is 353029.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-178153827-C-A is described in CliVar as Likely_benign. Clinvar id is 353029.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-178153827-C-A is described in CliVar as Likely_benign. Clinvar id is 353029.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-178153827-C-A is described in CliVar as Likely_benign. Clinvar id 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
NHP2	NM_017838.4 link	c.-10G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 4	ENST00000274606.8	NP_060308.1	Q9NX24
NHP2	NM_017838.4 link	c.-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
NHP2	ENST00000274606.8 link	c.-10G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 4	1	NM_017838.4	ENSP00000274606.4		Q9NX24
NHP2	ENST00000274606.8 link	c.-10G>T		5_prime_UTR_variant	Exon 1 of 4	1	NM_017838.4	ENSP00000274606.4		Q9NX24

Frequencies

GnomAD3 genomes

AF:

0.000309

AC:

AN:

152246

Hom.:

Cov.:

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:

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.:

Cov.:

AF XY:

0.000197

AC XY:

142

AN XY:

720840

show subpopulations

African (AFR)

AF:

0.000934

AC:

AN:

33192

American (AMR)

AF:

0.000422

AC:

AN:

42624

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25868

East Asian (EAS)

AF:

0.00

AC:

AN:

39022

South Asian (SAS)

AF:

0.0000118

AC:

AN:

84940

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52106

Middle Eastern (MID)

AF:

0.00157

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.000173

AC:

192

AN:

1106898

Other (OTH)

AF:

0.000518

AC:

AN:

59866

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

AN:

152364

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74514

show subpopulations

African (AFR)

AF:

0.000577

AC:

AN:

41590

American (AMR)

AF:

0.000523

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000176

AC:

AN:

68036

Other (OTH)

AF:

0.00378

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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.:

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

(source)

DANN

Benign

0.64

PhyloP100

-2.1

PromoterAI

-0.082

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=300/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over