Variant 17-63880827-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002059.5(GH2):c.401G>A(p.Ser134Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

GH2
NM_002059.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.49

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18867433).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GH2	NM_002059.5 linkuse as main transcript	c.401G>A	p.Ser134Asn	missense_variant	4/5	ENST00000423893.7	NP_002050.1	P01242-1A0A0M6L0J9
GH2	NM_022557.4 linkuse as main transcript	c.401G>A	p.Ser134Asn	missense_variant	4/4		NP_072051.1	P01242-2
GH2	NM_022558.4 linkuse as main transcript	c.401G>A	p.Ser134Asn	missense_variant	4/5		NP_072052.1	P01242-4
GH2	NM_022556.4 linkuse as main transcript	c.356G>A	p.Ser119Asn	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.401G>A	p.Ser134Asn	missense_variant	4/5	1	NM_002059.5	ENSP00000409294.2		P01242-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 20, 2024

The c.401G>A (p.S134N) alteration is located in exon 4 (coding exon 4) of the GH2 gene. This alteration results from a G to A substitution at nucleotide position 401, causing the serine (S) at amino acid position 134 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.081

BayesDel_noAF

Benign

-0.35

CADD

Benign

7.2

DANN

Benign

0.90

DEOGEN2

Benign

0.020

T;.;.;T;.

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.78

T;T;T;T;T

M_CAP

Benign

0.0041

MetaRNN

Benign

0.19

T;T;T;T;T

MetaSVM

Uncertain

-0.18

MutationAssessor

Uncertain

2.4

.;.;M;M;M

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.1

.;N;N;N;N

REVEL

Uncertain

0.30

Sift

Uncertain

0.018

.;D;D;T;D

Sift4G

Benign

0.082

T;T;D;T;D

Polyphen

0.076

.;.;.;B;.

Vest4

0.34

MutPred

0.42

.;.;Loss of disorder (P = 0.1272);Loss of disorder (P = 0.1272);Loss of disorder (P = 0.1272);

MVP

0.75

MPC

0.13

ClinPred

0.16

GERP RS

1.9

Varity_R

0.051

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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