chr7-27100560-T-C

Variant names:

• chr7-27100560-T-C
• rs886062265
• NM_006735.4:c.*166A>G

Variant summary

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

The NM_006735.4(HOXA2):​c.*166A>G 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HOXA2 NM_006735.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.214
• Publications: 0 publications found

Genes affected

HOXA2 (HGNC:5103): (homeobox A2) In vertebrates, the genes encoding the class of transcription factors called homeobox genes are found in clusters named A, B, C, and D on four separate chromosomes. Expression of these proteins is spatially and temporally regulated during embryonic development. This gene is part of the A cluster on chromosome 7 and encodes a DNA-binding transcription factor which may regulate gene expression, morphogenesis, and differentiation. The encoded protein may be involved in the placement of hindbrain segments in the proper location along the anterior-posterior axis during development. [provided by RefSeq, Jul 2008]

HOXA2 Gene-Disease associations (from GenCC):

• bilateral microtia-deafness-cleft palate syndrome

  Inheritance: AD, AR, SD Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
• microtia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000293629 (HGNC:):

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=-0.76).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006735.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXA2	NM_006735.4	MANE Select	c.*166A>G		3_prime_UTR	Exon 2 of 2	NP_006726.1	O43364

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXA2	ENST00000222718.7	TSL:1 MANE Select	c.*166A>G		3_prime_UTR	Exon 2 of 2	ENSP00000222718.5	O43364
	ENSG00000293629	ENST00000716605.1		n.310+4172T>C		intron	N/A
	ENSG00000293629	ENST00000716620.1		n.278+4172T>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 571918 Hom.: 0 Cov.: 8 AF XY: 0.00 AC XY: 0 AN XY: 303124

African (AFR) AF: 0.00 AC: 0 AN: 14466

American (AMR) AF: 0.00 AC: 0 AN: 21154

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15184

East Asian (EAS) AF: 0.00 AC: 0 AN: 32586

South Asian (SAS) AF: 0.00 AC: 0 AN: 50646

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37756

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2658

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 367290

Other (OTH) AF: 0.00 AC: 0 AN: 30178

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Bilateral microtia-deafness-cleft palate syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	12
DANN	Benign	0.81
PhyloP100		0.21

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: rs886062265; hg19: chr7-27140179;