2-47022084-T-A

Variant names:

• chr2-47022084-T-A
• rs587777551
• NM_020458.4:c.1510+105T>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 3P and 1B. PM2 PP5 BP4

The NM_020458.4(TTC7A):​c.1510+105T>A variant causes a intron 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. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TTC7A NM_020458.4 intron
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: -0.374
• Publications: 1 publications found

Genes affected

TTC7A (HGNC:19750): (tetratricopeptide repeat domain 7A) This gene encodes a protein containing tetratricopeptide repeats. Mutations in this gene disrupt intestinal development and can cause early onset inflammatory bowel disease and intestinal atresia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

TTC7A Gene-Disease associations (from GenCC):

• gastrointestinal defects and immunodeficiency syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• multiple intestinal atresia

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 2-47022084-T-A is Pathogenic according to our data. Variant chr2-47022084-T-A is described in ClinVar as Pathogenic. ClinVar VariationId is 140581.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83). . Strength limited to SUPPORTING due to the PP5.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020458.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC7A	NM_020458.4	MANE Select	c.1510+105T>A		intron	N/A	NP_065191.2
	TTC7A	NM_001288951.2		c.1510+105T>A		intron	N/A	NP_001275880.1
	TTC7A	NM_001288953.2		c.1408+105T>A		intron	N/A	NP_001275882.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC7A	ENST00000319190.11	TSL:2 MANE Select	c.1510+105T>A		intron	N/A	ENSP00000316699.5
	TTC7A	ENST00000394850.6	TSL:1	c.1510+105T>A		intron	N/A	ENSP00000378320.2
	TTC7A	ENST00000409825.5	TSL:1	n.*1259+105T>A		intron	N/A	ENSP00000386521.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 600796 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 315002

African (AFR) AF: 0.00 AC: 0 AN: 15968

American (AMR) AF: 0.00 AC: 0 AN: 28298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15684

East Asian (EAS) AF: 0.00 AC: 0 AN: 33854

South Asian (SAS) AF: 0.00 AC: 0 AN: 55296

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35436

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2266

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 382776

Other (OTH) AF: 0.00 AC: 0 AN: 31218

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Gastrointestinal defects and immunodeficiency syndrome 1 Pathogenic:1

Jan 02, 2014

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.3
DANN	Benign	0.67
PhyloP100		-0.37
Mutation Taster		=18/82	disease causing (ClinVar)

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: rs587777551; hg19: chr2-47249223;