chr17-63880878-T-G

Variant names:

• chr17-63880878-T-G
• rs1342142381
• NM_002059.5:c.350A>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_002059.5(GH2):​c.350A>C​(p.Gln117Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GH2 NM_002059.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.87

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.928

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GH2	NM_002059.5	c.350A>C	p.Gln117Pro	missense_variant	Exon 4 of 5	ENST00000423893.7	NP_002050.1
GH2	NM_022557.4	c.350A>C	p.Gln117Pro	missense_variant	Exon 4 of 4		NP_072051.1
GH2	NM_022558.4	c.350A>C	p.Gln117Pro	missense_variant	Exon 4 of 5		NP_072052.1
GH2	NM_022556.4	c.305A>C	p.Gln102Pro	missense_variant	Exon 4 of 5		NP_072050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GH2	ENST00000423893.7	c.350A>C	p.Gln117Pro	missense_variant	Exon 4 of 5	1	NM_002059.5	ENSP00000409294.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000712 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.14
CADD	Benign	22
DANN	Uncertain	0.97
DEOGEN2	Benign	0.13	T;.;.;D;.
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.96	D;D;D;D;D
M_CAP	Benign	0.026	D
MetaRNN	Pathogenic	0.93	D;D;D;D;D
MetaSVM	Uncertain	0.55	D
MutationAssessor	Pathogenic	3.7	.;.;H;H;H
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-4.9	.;D;D;D;D
REVEL	Uncertain	0.61
Sift	Uncertain	0.0010	.;D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;D;D
Polyphen		0.19	.;.;.;B;.
Vest4		0.84
MutPred		0.75		.;.;Loss of helix (P = 0.2022);Loss of helix (P = 0.2022);Loss of helix (P = 0.2022);
MVP		0.82
MPC		0.32
ClinPred		0.99	D
GERP RS		2.0
Varity_R		0.88
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1342142381; hg19: chr17-61958238;