8-38996464-C-G

Variant names:

• chr8-38996464-C-G
• rs7840270
• NM_078473.3:c.-25G>C

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.-25G>C variant causes a 5 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: 32)
• Consequence: TM2D2 NM_078473.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.906
• Publications: 23 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=-0.75).

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.-25G>C		5_prime_UTR	Exon 1 of 4	NP_510882.1	Q9BX73-1
	TM2D2	NM_001024380.2		c.-337G>C		5_prime_UTR	Exon 1 of 4	NP_001019551.1	Q9BX73-2
	TM2D2	NM_001024381.2		c.-236G>C		5_prime_UTR	Exon 1 of 4	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.-25G>C		5_prime_UTR	Exon 1 of 4	ENSP00000416050.2	Q9BX73-1
	TM2D2	ENST00000397070.6	TSL:1	c.-543G>C		5_prime_UTR	Exon 1 of 4	ENSP00000380260.2	Q9BX73-2
	TM2D2	ENST00000456845.6	TSL:1	c.-236G>C		5_prime_UTR	Exon 1 of 4	ENSP00000391674.2	Q9BX73-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 54

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	11
DANN	Benign	0.41
PhyloP100		0.91
PromoterAI		0.16	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs7840270; hg19: chr8-38853983;