rs3099

Variant names:

• chr2-219055032-G-A
• rs3099
• NM_002181.4:c.*175C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-219055032-G-A
• chr2-219055032-G-C
• chr2-219055032-G-T

Variant summary

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

The NM_002181.4(IHH):​c.*175C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IHH NM_002181.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.481
• Publications: 14 publications found

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 Gene-Disease associations (from GenCC):

• brachydactyly type A1

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• acrocapitofemoral dysplasia

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Orphanet

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 (BayesDel_noAF=-0.78).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IHH	NM_002181.4	c.*175C>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000295731.7	NP_002172.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IHH	ENST00000295731.7	c.*175C>T		3_prime_UTR_variant	Exon 3 of 3	1	NM_002181.4	ENSP00000295731.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 531372 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 276064

African (AFR) AF: 0.00 AC: 0 AN: 14004

American (AMR) AF: 0.00 AC: 0 AN: 20830

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14428

East Asian (EAS) AF: 0.00 AC: 0 AN: 31390

South Asian (SAS) AF: 0.00 AC: 0 AN: 47816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39546

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2188

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 332586

Other (OTH) AF: 0.00 AC: 0 AN: 28584

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.7
DANN	Benign	0.77
PhyloP100		0.48

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

Other links and lift over

dbSNP: rs3099; hg19: chr2-219919754;