5-178153819-G-C

Variant names:

• chr5-178153819-G-C
• rs1200196278
• ENST00000510363.1:n.66C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000510363.1(NHP2):​n.66C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,452,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NHP2 ENST00000510363.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.706
• Publications: 0 publications found

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

ENSG00000289726 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000510363.1. 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
	NHP2	NM_017838.4	MANE Select	c.-2C>G		5_prime_UTR	Exon 1 of 4	NP_060308.1
	NHP2	NM_001396110.1		c.-2C>G		5_prime_UTR	Exon 1 of 5	NP_001383039.1
	NHP2	NM_001034833.2		c.-2C>G		5_prime_UTR	Exon 1 of 3	NP_001030005.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NHP2	ENST00000510363.1	TSL:1	n.66C>G		non_coding_transcript_exon	Exon 1 of 2
	NHP2	ENST00000274606.8	TSL:1 MANE Select	c.-2C>G		5_prime_UTR	Exon 1 of 4	ENSP00000274606.4
	NHP2	ENST00000514354.5	TSL:3	c.-2C>G		5_prime_UTR	Exon 1 of 4	ENSP00000423803.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1452208 Hom.: 0 Cov.: 31 AF XY: 0.00000277 AC XY: 2 AN XY: 721958

African (AFR) AF: 0.00 AC: 0 AN: 33270

American (AMR) AF: 0.0000465 AC: 2 AN: 43016

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25884

East Asian (EAS) AF: 0.00 AC: 0 AN: 39172

South Asian (SAS) AF: 0.00 AC: 0 AN: 85206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52192

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107766

Other (OTH) AF: 0.00 AC: 0 AN: 59946

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.0
DANN	Benign	0.82
PhyloP100		-0.71
PromoterAI		-0.11	Neutral

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: rs1200196278; hg19: chr5-177580820;