17-63872867-G-T

Variant names:

• chr17-63872867-G-T
• rs1219707292
• NM_020991.4:c.259C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_020991.4(CSH2):​c.259C>A​(p.Pro87Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 12)
• Consequence: CSH2 NM_020991.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.46

Genes affected

CSH2 (HGNC:2441): (chorionic somatomammotropin hormone 2) The protein encoded by this gene is a member of the somatotropin/prolactin family of hormones and plays an important role in growth control. The gene is located at the growth hormone locus on chromosome 17 along with four other related genes in the same transcriptional orientation; an arrangement which is thought to have evolved by a series of gene duplications. Although the five genes share a remarkably high degree of sequence identity, they are expressed selectively in different tissues. Alternative splicing generates additional isoforms of each of the five growth hormones. This particular family member is expressed mainly in the placenta and utilizes multiple transcription initiation sites. Expression of the identical mature proteins for chorionic somatomammotropin hormones 1 and 2 is upregulated during development, while the ratio of 1 to 2 increases by term. Structural and expression differences provide avenues for developmental regulation and tissue specificity. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.936

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSH2	NM_020991.4	c.259C>A	p.Pro87Thr	missense_variant	Exon 3 of 5	ENST00000392886.7	NP_066271.1
CSH2	NM_022644.3	c.259C>A	p.Pro87Thr	missense_variant	Exon 3 of 4		NP_072170.1
CSH2	NM_022645.2	c.171+312C>A		intron_variant	Intron 2 of 2		NP_072171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSH2	ENST00000392886.7	c.259C>A	p.Pro87Thr	missense_variant	Exon 3 of 5	1	NM_020991.4	ENSP00000376623.2

Frequencies

GnomAD3 genomes Cov.: 12

GnomAD4 exome Cov.: 14

GnomAD4 genome Cov.: 12

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Uncertain	0.098	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.91	D;.;D
Eigen	Uncertain	0.31
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Benign	0.040	D
MetaRNN	Pathogenic	0.94	D;D;D
MetaSVM	Uncertain	0.61	D
MutationAssessor	Pathogenic	3.6	H;H;.
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-7.1	D;D;D
REVEL	Uncertain	0.57
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.0020	D;D;D
Vest4		0.76
MutPred		0.74		Gain of glycosylation at P87 (P = 0.0229);Gain of glycosylation at P87 (P = 0.0229);.;
MVP		0.60
ClinPred		0.97	D
GERP RS		3.7
Varity_R		0.76
gMVP		0.72

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: rs1219707292; hg19: chr17-61950227;