ENST00000332800.7:c.727C>T

Variant names:

• chr17-63880501-G-A
• ENST00000332800.7:c.727C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000332800.7(GH2):​c.727C>T​(p.Pro243Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: GH2 ENST00000332800.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.962
• Publications: 0 publications found

Genes affected

GH2 (HGNC:4262): (growth hormone 2) The protein encoded by this gene is a member of the somatotropin/prolactin family of hormones which play an important role in growth control. The gene, along with four other related genes, is located at the growth hormone locus on chromosome 17 where they are interspersed in the same transcriptional orientation; an arrangement which is thought to have evolved by a series of gene duplications. The five genes share a remarkably high degree of sequence identity. Alternative splicing generates additional isoforms of each of the five growth hormones, leading to further diversity and potential for specialization. As in the case of its pituitary counterpart, growth hormone 1, the predominant isoform of this particular family member shows similar somatogenic activity, with reduced lactogenic activity. Mutations in this gene lead to placental growth hormone/lactogen deficiency. [provided by RefSeq, Jul 2008]

ENSG00000303037 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20687786).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000332800.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GH2	NM_002059.5	MANE Select	c.474C>T	p.Ser158Ser	synonymous	Exon 5 of 5	NP_002050.1	P01242-1
	GH2	NM_022557.4		c.727C>T	p.Pro243Ser	missense	Exon 4 of 4	NP_072051.1	P01242-2
	GH2	NM_022558.4		c.470C>T	p.Ala157Val	missense	Exon 5 of 5	NP_072052.1	P01242-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GH2	ENST00000332800.7	TSL:1	c.727C>T	p.Pro243Ser	missense	Exon 4 of 4	ENSP00000333157.7	P01242-2
	GH2	ENST00000456543.6	TSL:1	c.470C>T	p.Ala157Val	missense	Exon 5 of 5	ENSP00000394122.2	P01242-4
	GH2	ENST00000423893.7	TSL:1 MANE Select	c.474C>T	p.Ser158Ser	synonymous	Exon 5 of 5	ENSP00000409294.2	P01242-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461596 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 727108

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111780

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	2.2
DANN	Uncertain	1.0
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.51	T
PhyloP100		0.96
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.16
Sift	Uncertain	0.014	D
Sift4G	Benign	0.090	T
Vest4		0.12
MutPred		0.43		Gain of loop (P = 0.0435)
MVP		0.35
ClinPred		0.56	D
GERP RS		-0.66

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

hg19: chr17-61957861;