chr8-38995750-C-A

Variant names:

• chr8-38995750-C-A
• rs7006414
• ENST00000397070.6:c.-247G>T

Variant summary

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

The ENST00000397070.6(TM2D2):​c.-247G>T variant causes a 5 prime UTR premature start codon gain 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: TM2D2 ENST00000397070.6 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.778
• Publications: 8 publications found

Genes affected

TM2D2 (HGNC:24127): (TM2 domain containing 2) The protein encoded by this gene contains a structural module related to that of the seven transmembrane domain G protein-coupled receptor superfamily. This protein has sequence and structural similarities to the beta-amyloid binding protein (BBP), but, unlike BBP, it does not regulate a response to beta-amyloid peptide. This protein may have regulatory roles in cell death or proliferation signal cascades. This gene has multiple alternatively spliced transcript variants which encode two different isoforms. [provided by RefSeq, Jul 2008]

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=-0.65).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TM2D2	NM_078473.3	c.228-345G>T		intron_variant	Intron 1 of 3	ENST00000456397.7	NP_510882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TM2D2	ENST00000456397.7	c.228-345G>T		intron_variant	Intron 1 of 3	1	NM_078473.3	ENSP00000416050.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1114300 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 530130

African (AFR) AF: 0.00 AC: 0 AN: 22718

American (AMR) AF: 0.00 AC: 0 AN: 10804

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14556

East Asian (EAS) AF: 0.00 AC: 0 AN: 23804

South Asian (SAS) AF: 0.00 AC: 0 AN: 35074

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20266

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3016

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 938974

Other (OTH) AF: 0.00 AC: 0 AN: 45088

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	2.4
DANN	Benign	0.83
PhyloP100		-0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs7006414; hg19: chr8-38853269;