chr17-63880868-C-G

Position:

chr17-63880868-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002059.5(GH2):c.360G>C(p.Arg120Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000781 in 1,614,064 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000079 ( 2 hom. )

Consequence

GH2
NM_002059.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.94

Variant links:

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]

GH2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06099981).

BP6

Variant 17-63880868-C-G is Benign according to our data. Variant chr17-63880868-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2223410.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GH2	NM_002059.5 linkuse as main transcript	c.360G>C	p.Arg120Ser	missense_variant	4/5	ENST00000423893.7	NP_002050.1	P01242-1A0A0M6L0J9
GH2	NM_022557.4 linkuse as main transcript	c.360G>C	p.Arg120Ser	missense_variant	4/4		NP_072051.1	P01242-2
GH2	NM_022558.4 linkuse as main transcript	c.360G>C	p.Arg120Ser	missense_variant	4/5		NP_072052.1	P01242-4
GH2	NM_022556.4 linkuse as main transcript	c.315G>C	p.Arg105Ser	missense_variant	4/5		NP_072050.1	P01242-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GH2	ENST00000423893.7 linkuse as main transcript	c.360G>C	p.Arg120Ser	missense_variant	4/5	1	NM_002059.5	ENSP00000409294.2		P01242-1

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

GnomAD3 exomes

AF:

0.0000517

AC:

AN:

251402

Hom.:

AF XY:

0.0000589

AC XY:

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000967

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000787

AC:

115

AN:

1461816

Hom.:

Cov.:

AF XY:

0.0000825

AC XY:

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000962

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

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:

0.00

Alfa

AF:

0.0000992

Hom.:

Bravo

AF:

0.0000718

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000107

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 16, 2021

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

0.16

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.41

CADD

Benign

1.8

DANN

Benign

0.53

DEOGEN2

Benign

0.0028

T;.;.;T;.

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.82

T;T;T;T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.061

T;T;T;T;T

MetaSVM

Benign

-0.47

MutationAssessor

Benign

-0.41

.;.;N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

0.69

.;N;N;N;N

REVEL

Benign

0.22

Sift

Benign

1.0

.;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.0010

.;.;.;B;.

Vest4

0.29

MutPred

0.67

.;.;Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);

MVP

0.53

MPC

0.097

ClinPred

0.014

GERP RS

2.1

Varity_R

0.061

gMVP

0.33

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over