NM_002059.5:c.*115G>C

Variant names:

• chr17-63880206-C-G
• rs57561325
• NM_002059.5:c.*115G>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002059.5(GH2):​c.*115G>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00301 in 1,567,876 control chromosomes in the GnomAD database, including 130 homozygotes. 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: 𝑓 0.016 (68 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (62 hom.)
• Consequence: GH2 NM_002059.5 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.375

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GH2	NM_002059.5	c.*115G>C		downstream_gene_variant		ENST00000423893.7	NP_002050.1
GH2	NM_022557.4	c.*251G>C		downstream_gene_variant			NP_072051.1
GH2	NM_022558.4	c.*27G>C		downstream_gene_variant			NP_072052.1
GH2	NM_022556.4	c.*115G>C		downstream_gene_variant			NP_072050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GH2	ENST00000423893.7	c.*115G>C		downstream_gene_variant		1	NM_002059.5	ENSP00000409294.2

Frequencies

GnomAD3 genomes AF: 0.0161 AC: 2442 AN: 151974 Hom.: 68 Cov.: 32

Gnomad AFR AF: 0.0557

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00635

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: 0.000162

Gnomad OTH AF: 0.0144

GnomAD3 exomes AF: 0.00365 AC: 723 AN: 198042 Hom.: 18 AF XY: 0.00284 AC XY: 303 AN XY: 106804

Gnomad AFR exome AF: 0.0578

Gnomad AMR exome AF: 0.00225

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000149

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000948

Gnomad OTH exome AF: 0.00154

GnomAD4 exome AF: 0.00161 AC: 2275 AN: 1415784 Hom.: 62 Cov.: 30 AF XY: 0.00139 AC XY: 975 AN XY: 700412

Gnomad4 AFR exome AF: 0.0594

Gnomad4 AMR exome AF: 0.00256

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000133

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000544

Gnomad4 OTH exome AF: 0.00324

GnomAD4 genome AF: 0.0161 AC: 2445 AN: 152092 Hom.: 68 Cov.: 32 AF XY: 0.0152 AC XY: 1130 AN XY: 74356

Gnomad4 AFR AF: 0.0556

Gnomad4 AMR AF: 0.00635

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.0143

Alfa AF: 0.00884 Hom.: 2

Bravo AF: 0.0187

Asia WGS AF: 0.00433 AC: 16 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	12
DANN	Benign	0.26

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs57561325; hg19: chr17-61957566;