chr17-63880842-T-A

Position:

• chr17-63880842-T-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_002059.5(GH2):​c.386A>T​(p.Tyr129Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GH2 NM_002059.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.62

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06929138).
• BP6: Variant 17-63880842-T-A is Benign according to our data. Variant chr17-63880842-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 2270801.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GH2	NM_002059.5	c.386A>T	p.Tyr129Phe	missense_variant	4/5	ENST00000423893.7
GH2	NM_022557.4	c.386A>T	p.Tyr129Phe	missense_variant	4/4
GH2	NM_022558.4	c.386A>T	p.Tyr129Phe	missense_variant	4/5
GH2	NM_022556.4	c.341A>T	p.Tyr114Phe	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GH2	ENST00000423893.7	c.386A>T	p.Tyr129Phe	missense_variant	4/5	1	NM_002059.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 07, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	5.4
DANN	Benign	0.33
DEOGEN2	Benign	0.0055	T;.;.;T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.050	N
LIST_S2	Uncertain	0.88	D;D;D;D;D
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.069	T;T;T;T;T
MetaSVM	Benign	-0.36	T
MutationAssessor	Benign	0.59	.;.;N;N;N
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.78	.;N;N;N;N
REVEL	Uncertain	0.33
Sift	Benign	1.0	.;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T
Polyphen		0.0	.;.;.;B;.
Vest4		0.27
MutPred		0.48		.;.;Loss of solvent accessibility (P = 0.0022);Loss of solvent accessibility (P = 0.0022);Loss of solvent accessibility (P = 0.0022);
MVP		0.17
MPC		0.27
ClinPred		0.11	T
GERP RS		0.73
Varity_R		0.11
gMVP		0.26

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-61958202;