rs763776483

Variant names:

• chr17-63880636-C-T
• rs763776483
• ENST00000332800.7:c.592G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-63880636-C-T
• chr17-63880636-C-A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_022557.4(GH2):​c.592G>A​(p.Val198Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: GH2 NM_022557.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.881
• Publications: 0 publications found

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]

ENSG00000303037 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049360335).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022557.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GH2	NM_002059.5	MANE Select	c.457-118G>A		intron	N/A	NP_002050.1	P01242-1
	GH2	NM_022557.4		c.592G>A	p.Val198Met	missense	Exon 4 of 4	NP_072051.1	P01242-2
	GH2	NM_022558.4		c.453-118G>A		intron	N/A	NP_072052.1	P01242-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GH2	ENST00000332800.7	TSL:1	c.592G>A	p.Val198Met	missense	Exon 4 of 4	ENSP00000333157.7	P01242-2
	GH2	ENST00000423893.7	TSL:1 MANE Select	c.457-118G>A		intron	N/A	ENSP00000409294.2	P01242-1
	GH2	ENST00000456543.6	TSL:1	c.453-118G>A		intron	N/A	ENSP00000394122.2	P01242-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000159 AC: 4 AN: 251462 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000867

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461780 Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5 AN XY: 727196

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.0000671 AC: 3 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111932

Other (OTH) AF: 0.0000166 AC: 1 AN: 60388

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.13
DANN	Benign	0.83
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0032	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-0.74	T
PhyloP100		-0.88
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.46	N
REVEL	Benign	0.17
Sift	Benign	0.12	T
Sift4G	Benign	0.14	T
Vest4		0.042
MutPred		0.17		Loss of catalytic residue at V198 (P = 0.0544)
MVP		0.040
MPC		0.078
ClinPred		0.033	T
GERP RS		-5.5
gMVP		0.12

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

Other links and lift over

dbSNP: rs763776483; hg19: chr17-61957996;