Variant 2-219055315-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000295731.7(IHH):c.1128T>C(p.Thr376=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.815 in 1,612,922 control chromosomes in the GnomAD database, including 537,795 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.86 ( 56256 hom., cov: 35)

Exomes 𝑓: 0.81 ( 481539 hom. )

Consequence

IHH
ENST00000295731.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.798

Variant links:

Genes affected

IHH (HGNC:5956): (Indian hedgehog signaling molecule) This gene encodes a member of the hedgehog family of proteins. The encoded preproprotein is proteolytically processed to generate multiple protein products, including an N-terminal fragment that is involved in signaling. Hedgehog family proteins are essential secreted signaling molecules that regulate a variety of developmental processes including growth, patterning and morphogenesis. The protein encoded by this gene specifically plays a role in bone growth and differentiation. Mutations in this gene are the cause of brachydactyly type A1, which is characterized by shortening or malformation of the fingers and toes. Mutations in this gene are also the cause of acrocapitofemoral dysplasia. [provided by RefSeq, Nov 2015]

IHH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 2-219055315-A-G is Benign according to our data. Variant chr2-219055315-A-G is described in ClinVar as [Benign]. Clinvar id is 593247.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.798 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IHH	NM_002181.4 linkuse as main transcript	c.1128T>C	p.Thr376=	synonymous_variant	3/3	ENST00000295731.7	NP_002172.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IHH	ENST00000295731.7 linkuse as main transcript	c.1128T>C	p.Thr376=	synonymous_variant	3/3	1	NM_002181.4	ENSP00000295731	P1

Frequencies

GnomAD3 genomes

AF:

0.856

AC:

130272

AN:

152186

Hom.:

56199

Cov.:

show subpopulations

Gnomad AFR

AF:

0.961

Gnomad AMI

AF:

0.707

Gnomad AMR

AF:

0.836

Gnomad ASJ

AF:

0.749

Gnomad EAS

AF:

0.907

Gnomad SAS

AF:

0.822

Gnomad FIN

AF:

0.875

Gnomad MID

AF:

0.718

Gnomad NFE

AF:

0.801

Gnomad OTH

AF:

0.828

GnomAD3 exomes

AF:

0.835

AC:

207168

AN:

248116

Hom.:

86872

AF XY:

0.829

AC XY:

111703

AN XY:

134794

show subpopulations

Gnomad AFR exome

AF:

0.965

Gnomad AMR exome

AF:

0.867

Gnomad ASJ exome

AF:

0.749

Gnomad EAS exome

AF:

0.919

Gnomad SAS exome

AF:

0.813

Gnomad FIN exome

AF:

0.878

Gnomad NFE exome

AF:

0.800

Gnomad OTH exome

AF:

0.796

GnomAD4 exome

AF:

0.811

AC:

1184656

AN:

1460618

Hom.:

481539

Cov.:

AF XY:

0.810

AC XY:

588270

AN XY:

726596

show subpopulations

Gnomad4 AFR exome

AF:

0.962

Gnomad4 AMR exome

AF:

0.859

Gnomad4 ASJ exome

AF:

0.749

Gnomad4 EAS exome

AF:

0.877

Gnomad4 SAS exome

AF:

0.813

Gnomad4 FIN exome

AF:

0.876

Gnomad4 NFE exome

AF:

0.801

Gnomad4 OTH exome

AF:

0.813

GnomAD4 genome

AF:

0.856

AC:

130387

AN:

152304

Hom.:

56256

Cov.:

AF XY:

0.859

AC XY:

64010

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.961

Gnomad4 AMR

AF:

0.835

Gnomad4 ASJ

AF:

0.749

Gnomad4 EAS

AF:

0.908

Gnomad4 SAS

AF:

0.822

Gnomad4 FIN

AF:

0.875

Gnomad4 NFE

AF:

0.801

Gnomad4 OTH

AF:

0.828

Alfa

AF:

0.809

Hom.:

63417

Bravo

AF:

0.858

Asia WGS

AF:

0.840

AC:

2920

AN:

3478

EpiCase

AF:

0.786

EpiControl

AF:

0.790

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 31, 2018	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Acrocapitofemoral dysplasia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.8

DANN

Benign

0.58

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