8-38996101-G-C

Variant names:

• chr8-38996101-G-C
• rs6991968
• NM_078473.3:c.227+112C>G

Variant summary

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

The NM_078473.3(TM2D2):​c.227+112C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000664 in 150,654 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TM2D2 NM_078473.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.205
• Publications: 7 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=-0.87).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_078473.3. 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
	TM2D2	NM_078473.3	MANE Select	c.227+112C>G		intron	N/A	NP_510882.1	Q9BX73-1
	TM2D2	NM_001024380.2		c.-291-307C>G		intron	N/A	NP_001019551.1	Q9BX73-2
	TM2D2	NM_001024381.2		c.-191+318C>G		intron	N/A	NP_001019552.1	Q9BX73-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TM2D2	ENST00000456397.7	TSL:1 MANE Select	c.227+112C>G		intron	N/A	ENSP00000416050.2	Q9BX73-1
	TM2D2	ENST00000397070.6	TSL:1	c.-292+112C>G		intron	N/A	ENSP00000380260.2	Q9BX73-2
	TM2D2	ENST00000456845.6	TSL:1	c.-191+318C>G		intron	N/A	ENSP00000391674.2	Q9BX73-2

Frequencies

GnomAD3 genomes AF: 0.00000664 AC: 1 AN: 150528 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1140192 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 559664

African (AFR) AF: 0.00 AC: 0 AN: 25634

American (AMR) AF: 0.00 AC: 0 AN: 21904

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18274

East Asian (EAS) AF: 0.00 AC: 0 AN: 34346

South Asian (SAS) AF: 0.00 AC: 0 AN: 61868

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42028

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4916

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 882632

Other (OTH) AF: 0.00 AC: 0 AN: 48590

GnomAD4 genome AF: 0.00000664 AC: 1 AN: 150654 Hom.: 0 Cov.: 32 AF XY: 0.0000136 AC XY: 1 AN XY: 73652

African (AFR) AF: 0.00 AC: 0 AN: 40130

American (AMR) AF: 0.00 AC: 0 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10568

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67964

Other (OTH) AF: 0.00 AC: 0 AN: 2098

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.9
DANN	Benign	0.49
PhyloP100		-0.20
PromoterAI		-0.011	Neutral

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: rs6991968; hg19: chr8-38853620;