Variant 17-63872128-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM4BP6_Very_StrongBS2

The NM_020991.4(CSH2):c.652T>C(p.Ter218GlnextTer?) variant causes a stop lost change. The variant allele was found at a frequency of 0.00425 in 1,614,102 control chromosomes in the GnomAD database, including 70 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0030 ( 3 hom., cov: 29)

Exomes 𝑓: 0.0044 ( 67 hom. )

Consequence

CSH2
NM_020991.4 stop_lost

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 6.01

Variant links:

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]

CSH2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

PM4

Stoplost variant in NM_020991.4 Downstream stopcodon found after 65 codons.

BP6

Variant 17-63872128-A-G is Benign according to our data. Variant chr17-63872128-A-G is described in ClinVar as [Benign]. Clinvar id is 717494.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CSH2	NM_020991.4 linkuse as main transcript	c.652T>C	p.Ter218GlnextTer?	stop_lost	5/5	ENST00000392886.7	NP_066271.1
CSH2	NM_022645.2 linkuse as main transcript	c.367T>C	p.Ter123GlnextTer?	stop_lost	3/3		NP_072171.1
CSH2	NM_022644.3 linkuse as main transcript	c.*401T>C		3_prime_UTR_variant	4/4		NP_072170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSH2	ENST00000392886.7 linkuse as main transcript	c.652T>C	p.Ter218GlnextTer?	stop_lost	5/5	1	NM_020991.4	ENSP00000376623	P1	P0DML3-1

Frequencies

GnomAD3 genomes

AF:

0.00301

AC:

458

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000675

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00584

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00490

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00358

AC:

901

AN:

251390

Hom.:

AF XY:

0.00339

AC XY:

460

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.000800

Gnomad AMR exome

AF:

0.00176

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00137

Gnomad FIN exome

AF:

0.00721

Gnomad NFE exome

AF:

0.00535

Gnomad OTH exome

AF:

0.00326

GnomAD4 exome

AF:

0.00438

AC:

6401

AN:

1461818

Hom.:

Cov.:

AF XY:

0.00419

AC XY:

3047

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.000568

Gnomad4 AMR exome

AF:

0.00181

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00181

Gnomad4 FIN exome

AF:

0.00721

Gnomad4 NFE exome

AF:

0.00497

Gnomad4 OTH exome

AF:

0.00384

GnomAD4 genome

AF:

0.00301

AC:

458

AN:

152284

Hom.:

Cov.:

AF XY:

0.00313

AC XY:

233

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.000673

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00584

Gnomad4 NFE

AF:

0.00490

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00398

Hom.:

Bravo

AF:

0.00272

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00500

AC:

ExAC

AF:

0.00368

AC:

447

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00311

EpiControl

AF:

0.00356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 15, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.67

Eigen

Pathogenic

0.78

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Pathogenic

0.98

MutationTaster

Benign

1.0

D;N;N;N

Vest4

0.30

GERP RS

4.0

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

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