GeneBe

rs2796

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002820.3(PTHLH):​c.*166G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

PTHLH
NM_002820.3 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.96

Publications

12 publications found
Variant links:
Genes affected
PTHLH (HGNC:9607): (parathyroid hormone like hormone) The protein encoded by this gene is a member of the parathyroid hormone family. This hormone, via its receptor, PTHR1, regulates endochondral bone development and epithelial-mesenchymal interactions during the formation of the mammary glands and teeth. It is responsible for most cases of humoral hypercalcemia of malignancy, and mutations in this gene are associated with brachydactyly type E2 (BDE2). Alternatively spliced transcript variants have been found for this gene. There is also evidence for alternative translation initiation from non-AUG (CUG and GUG) start sites, downstream of the initiator AUG codon, resulting in nuclear forms of this hormone. [provided by RefSeq, Nov 2013]
PTHLH Gene-Disease associations (from GenCC):
  • brachydactyly type E2
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
  • brachydactyly type E
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002820.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
PTHLH
NM_198965.2
MANE Select
c.524+170G>T
intron
N/ANP_945316.1P12272-1
PTHLH
NM_002820.3
c.*166G>T
3_prime_UTR
Exon 4 of 4NP_002811.1P12272-2
PTHLH
NM_198964.2
c.*166G>T
3_prime_UTR
Exon 3 of 3NP_945315.1P12272-2

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
PTHLH
ENST00000395868.7
TSL:1
c.*166G>T
3_prime_UTR
Exon 3 of 3ENSP00000379209.3P12272-2
PTHLH
ENST00000535992.5
TSL:1
c.*166G>T
3_prime_UTR
Exon 3 of 3ENSP00000440613.1P12272-2
PTHLH
ENST00000545234.6
TSL:5 MANE Select
c.524+170G>T
intron
N/AENSP00000441765.1P12272-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1347216
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
659882
African (AFR)
AF:
0.00
AC:
0
AN:
30908
American (AMR)
AF:
0.00
AC:
0
AN:
33352
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
22688
East Asian (EAS)
AF:
0.00
AC:
0
AN:
35386
South Asian (SAS)
AF:
0.00
AC:
0
AN:
71312
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
33484
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3878
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1059976
Other (OTH)
AF:
0.00
AC:
0
AN:
56232
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.00
Hom.:
260

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
1.5
DANN
Benign
0.80
PhyloP100
-3.0

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: rs2796; hg19: chr12-28116111; API